N E W S L E T T E R - Hinduja Hospital...Dr. Kunal Sehgal, Dr. Neha Lankhe Hematology Department Let...

N E W S L E T T E R

ORGAN SPECIFIC AUTOIMMUNE DISEASES

2014 Volume 27 No.1

EditorDr. Reeta J. Dalal

Guest Editor Dr. C. Balakrishnan

Editorial Board

Dr. Philip Abraham

Dr. Tester Ashavaid

Dr. C. Balakrishnan

Dr. Sudeep Shah

Printed & Published at:P D Hinduja National Hospital & Medical Research CentreVeer Savarkar Marg, Mahim, Mumbai – 400016. (INDIA)Tel.: +91-22-2445 1515/ 2444 2222/ 2444 9199 Fax: +91-22-24449151Website: www.hindujahospital.com

For Editorial Enquiries write to us at: [email protected]

11

15

18

25

5

22

31

32

33

38

27

4 Guest Editor Dr. C. Balakrishnan

'When RBC Develop Cold Feet'Cold Agglutinin Disease and the role of the neglected parameter MCHCDr. Kunal Sehgal

Gut-specific Autoimmune DiseasesDr. Philip Abraham

Primary Autoimmune Neurological DisordersDr. Roopkumar Gursahani

Auto Immune Diseases&Ocular ManifestationsDr. Nisheeta Agarwala

Autoimmune Diseases of the SkinDr. Nina Madnani

Adverse Effects of Immunosuppressive TherapyDr. Gurmeet Mangat

Laboratory Tests in RheumatologyDr. Rohini Samant

On the trail of diseases, years before they strike - Auto antibodiesDr. Vipla Puri

Rheumatology QuizDr. C. Balakrishnan

Our Team

P. D. Hinduja News

Welcome to P. D. Hinduja Hospital Pariwar

34

Editor EmeritusDr. V. R. Joshi

Immune system protects us

from disease and infection.

When immune response is

generated against self-

components autoimmune

d i s e a s e s r e s u l t .

Au to immune d i seases

frequently pose a challenge in diagnosis and

treatment hence their knowledge is essential in

clinical practice. The Rheumatology team together

with other specialists have contributed towards this

Newsletter issue on "Organ Specific Autoimmune

Diseases". We are privileged to have Dr. V. R. Joshi,

Emeritus Editor of Hinduja Newsletter to write the

preface for this issue.

Dr. Reeta J. Dalal

Consultant Physician

2014 Volume 27 No.12

Page No.

PREFACE


The primary function of immune system is to protect

an individual from infection. It achieves this by

identifying the invading organism and destroying it

employing its (versatile) (awesome!) destructive

machinery. Immune system harbours the potential to

attack and destroy the host cells and tissues. This is

prevented by the induction of self-tolerance which is

achieved by eliminating cells with self reactive

potential. The elimination takes place during immune

cell maturation process in the thymus (T-cells) and bone-marrow (B-cells).

However, the elimination process is not perfect and a few weakly self reactive

cells escape the elimination process. These elements have the potential to

induce autoimmunity.

The development of autoimmunity however needs additional factors, namely

genetic susceptibility (to develop autoimmunity) and inciting environmental

agent(s) usually a microorganism. Once initiated the process becomes self-

perpetuating, as the cellular destruction provides constant supply of antigens

against which autoimmunity has developed. Hence, autoimmune diseases

are persistent, incurable, associated with significant ill health and even early

death. Autoimmune process can be organ specific e.g. Hahimoto's thyroiditis

or diffuse and non organ specific e.g. systemic lupus erythematosus. Being

incurable, and with serious health issues, early diagnosis and initiation of

appropriate therapy (to control the disease) is of paramount importance.

Treatment involves corticosteroids (almost always in most situations) along

with chemotherapy with immunosuppressive drugs and recently with

biologics. Failure of treatment results in organ failure often necessitating

replacement therapy including organ transplantation.

This edition of the Newsletter provides information on organ specific

autoimmune disorders.

Dr. V. R. JoshiM. D., Consultant Rheumatologist

and Director, Research, FICP (India)


Guest Editor

Dr. C. BalakrishnanMD, Consultant Rheumatologist

Autoimmune diseases are a group of diseases where

the immune system turns on itself and causes

pathology to self- tissues. Systemic auto-immune

diseases like Rheumatoid arthritis and Systemic Lupus

eythematosus are diseases that are being increasingly

recognized.

Autoimmune diseases limited to organs are also

common and increasingly seen and diagnosed. It is important to recognize

these diseases as their treatment includes the usage of steroids and other

immunosuppressive therapy.

This issue is dedicated to “Organ specific auto-immune diseases” afflicting

different organs systems. I hope it will enable the reader to familiarize himself

and approach these patients in a better way.

'When RBC Develop Cold Feet’Cold Agglutinin Disease and the role of the neglected

parameter MCHC

Dr. Kunal Sehgal, Dr. Neha LankheHematology Department

Let us start by looking at Complete Blood Count (CBC) results of cases 1 and 2 shown in Table 1. At the outset, the striking thing is that there is a hemoglobin (Hb) and hematocrit (HCT) mismatch. Normally HCT = 3 x Hb. However, in the above scenario this relationship is not maintained. This may rarely occur if sample is kept on table for a long time and sample run on a machine without mixing. However in current day automated analysers with vacutainer collections, sample is automatically mixed 8-10 times before aspiration as was done in the two cases shown in Table 1.

Table 1: CBC reports of cases 1 and 2 with Reference ranges

9 9 9PC 680 X 10 316 X 10 150 - 400 X 10 /L

CBC Parameter Case 1 Case 2 Reference range

12 12 12RBC 0.84 X 10 0.86 X 10 4.5 - 6.5 X 10 /L

Hb 7.3 7.9 13 - 18 g/dl

HCT 8.2 10.1 40 - 54

MCV 97.6 117.4 76 - 96 fl

MCH 86.9 91.9 27 - 32pg

MCHC 89 78.2 30 - 36 g/dl

RDW 20 28.2 11.5 - 14.5 %

9 9TLC 8 X 10 12.44 X 10 4 - 11 X 109 /L

Having known that there is nothing wrong with the machine the next striking result is the abnormally high MCV and MCHC. The MCHC i.e. the Mean Cell Hemoglobin Concentration is a derived parameter in the automated analysers. It is derived from the Hb and HCT according to the formula: MCHC=(Hb/ HCT) x100.

Typically, MCHC remains in normal range in most anemias as both Hb and HCT are proportionately

reduced. In Iron Deficiency anemias it is on the lower side of normal whereas in macrocytic anemias it is on the higher side of normal. A MCHC reading of > 36 is an uncommon finding and should alarm the CBC operator.

The MCHC is known to >36 in hereditary spherocytosis (HS). However all cases of HS may not have MCHC >36 and typically MCHC because of spherocytosis will not exceed 40. A high MCHC as shown in cases above is typically seen when the red cells have agglutinated.

The agglutinated RBCs get counted together as one large RBC, which explains the falsely low RBC count and the high MCV, high MCH and the high MCHC. As Hb is measured after lysing of RBCs, the Hb measurement is correct but RBC count and HCT is falsely low. MCHC falsely increases as numerator (Hb) remains the same but denominator is markedly reduced (HCT). Hence, if the MCHC is high (>36 g/dl), peripheral smear of the sample must be examined for


presence of spherocytes or red cell agglutinates. If the latter are found, the sample is kept in a water bath at 37ºC for an hour and re-analysed. Correction of RBC count and indices and reduction or disappearance of agglutinates on smear after warming of sample suggests presence of cold agglutinins in the serum. As a policy all samples in our laboratory with MCHC>36

Case 1 Case 2 CBC Parameters

Pre-warming Post-warming Pre-warming Post-warming

12 12 12 12RBC 0.84 X 10 2.42 X 10 0.86 X 10 1.53 X 10

Hb 7.3 8.3 7.9 8.0

HCT 8.2 22.6 10.1 17.8

MCV 97.6 93.5 117.4 116.3

MCH 86.9 34.2 91.9 52.3

MCHC 89 36.2 78.2 44.9

are re-run after one hour of warming at 37ºC in a water bath.

Coming back to our index cases, the smears of both the samples (cases 1 and 2) revealed red cell agglutinates (Figure 1) and hence post-warming sample were analysed which showed the following results:

Red cell agglutinates seen on peripheral smear

In case 1, all the RBC indices now show correction post warming. In case 2, there is a partial correction only and the smear showed RBC agglutinates even after post warming, however the agglutination was much reduced in severity. A work-up for cold agglutinin disease was advised in both the cases.

Both case 1 and case 2 showed similar CBC findings but had contrasting clinical profile as discussed below.

Case 1:This was a 43 year old female who presented and fever with chills since three weeks, cough with expectoration and yellowish discoloration of urine. There was no history of abdominal pain, clay colored stools, dyspnea, oliguria or joint pain. She was diagnosed to have malaria and treated for the same, however, fever persisted. On examination, icterus was present, vitals were stable and liver was soft, non-tender and mildly enlarged. In addition to the CBC findings, discussed earlier, other laboratory investigations revealed:

� Reticulocyte count 10.8%

� Total bilirubin 7.1 mg/dL (Direct: 4, Indirect: 3.1)

� SGOT 101 IU (9-36) ; SGPT 39 IU (10-40)

� ALP 303 IU (40-120) ; GGT 331 IU (0-60)

� CRP 192 mg/ dL


Cold Agglutinin Disease and the role of the neglected parameter MCHC'When RBC Develop Cold Feet’

Chest X ray revealed fibrotic shadows in the right upper zone, fibronodular shadows in the left upper zone with left apical pleural thickening. In view of the presence of cold agglutinins on peripheral smear, clinical history of a febrile patient with suspected interstitial shadows on chest X-rays, work up for mycoplasma pneumoniae was advised. Anti M.Pneumoniae IgM was positive 16.77 NTU (>11 is positive). Bacterial cultures were negative.

Case 2

This was an 89 year old female, known case of hypertension with ischemic heart disease and severe osteoarthritis, who presented with a history of traumatic fall with subsequent fracture of right femoral neck, superior and inferior pubic rami. Laboratory investigations revealed:

� Total bilirubin 2.8 mg/dL (Direct: 2.5, Indirect: 0.3)

� SGOT 15 IU (9-36) SGPT 11 IU (10-40)

� ALP 54 (40-120) GGT 6 (0-60)

� Total serum proteins 6.1g/dL (albumin 3,globulin 3.1)

� Reticulocyte count 10.1%

� Renal function tests normal

� Coagulation profile normal

During Blood grouping and cross matching blood for surgery, RBC antibody screening was positive, Direct Coombs test was positive. In addition as discussed earlier the CBC showed presence of RBC agglutinates on the peripheral smear. Hence, the presence of a cold antibody was confirmed and a search to rule out malignancy and/ or infection was done.

� Anti Mycoplasm Pneumoniae IgM was negative

(2.395 NTU) � Immunofixation electrophoresis revealed a

monoclonal gammopathy of IgM kappa type. � Serum kappa light chain: 1620 mg/dL (629-1350)

� Serum lambda light chain: 562 mg/dL (313-723) � Kappa: lambda ratio was 2.88 (1.47-2.95).� Bence Jones proteins were absent in urine.

� Bone marrow examination revealed a hyper-

cellular marrow with 18% lymphocytes which on flow cytometric immunophenotyping comprised of

kappa restricted B cells expressing CD 19, CD 20, CD 22 and heterogenous FMC7 while they were negative for CD5, CD10, CD23, CD11c, CD103, Cd25, CD123, CD2, CD3, CD4, CD7 and CD8.

Thus, a diagnosis of CD5, CD10 negative B cell NHL was offered. In view of the IgM kappa band on IFE, the diagnosis was consistent with a lymphoplasmacytic lymphoma.

Cold Agglutinin Disease

Introduction

Cold hemagglutination was first described by Landsteiner in 1903. Cold agglutination disease (CAD) is a type of autoimmune hemolytic anemia (AIHA) which is characterized by an immune reaction against red blood cell self-antigens. CAD has been classified into primary (idiopathic) and secondary.

Etiology:

Primary Cold Agglutinin Disease is usually associated with monoclonal cold-reacting autoantibodies, usually chronic and occurs after the fifth decade of life. Secondary Cold Agglutinin Disease is associated with infectious or lymphoproliferative disorders. Monoclonal secondary disease is usually chronic, occurs in adults, while polyclonal is usually transient and occurs in children and young adults.

Causes of the Secondary disease:

1. Neoplastic etiology � B-cell neoplasms - Waldenström

macroglobulinemia, Lymphoma, Chronic

Lymphoid Leukemia, Myeloma � Nonhematologic neoplasms

2. Infectious etiology � Mycoplasma infections -M. pneumoniae

� Viral infections - Infectious mononucleosis due to Epstein-Barr virus (EBV) or CMV, Mumps,

Varicella, Rubella, Adenovirus, HIV, Influenza,

Hepatitis C

� Bacterial infections - Legionnaire disease,

Syphilis, Listeriosis, Escherichia coli � Parasitic infections - Malaria, Trypanosomiasis

Pathogenesis:

Cold agglutinins may be found in the sera of healthy subjects as well as in patients with cold AIHA. Cold agglutinins bind to erythrocyte surface antigens at a temperature optimum of 0 to 4ºC. In contrast to polyclonal agglutinins in healthy individuals, monoclonal agglutinins often have high thermal amplitude, which contributes to their pathogenicity at temperatures approaching 37ºC. Benign cold



agglutinins occur in titers which are less than 1:64 at 4ºC and they have no activity at higher temperatures, while pathologic cold agglutinins typically have titers well over 1:1000 and they may react at 28 to 31ºC or even up to 37ºC.

In the great majority of CAD patients, the cold agglutinins are of the IgM kappa type and are specific for the I antigen, an erythrocyte surface carbohydrate macromolecule.

During passage through acral blood vessels, cooling allows IgM cold agglutinin to bind to erythrocytes, causing agglutination and binding of complement C1 complex. C1 esterase activates C4 and C2, generating C3 convertase which binds and splits C3, leading to deposition of C3b on the erythrocyte surface. Upon subsequent warming, IgM dissociates from the cell surface and the agglutinated cells are detached from each other, while C3b remains bound. C3b may in turn activate C5, leading to the formation of the membrane attack complex and intravascular cell lysis. Most destruction of C3b-coated erythrocytes is mediated by reticulo-endothelial cells in the liver. Intrahepatic conversion of C3b is responsible for the deposition of C3d on the surviving erythrocytes which are released into the systemic circulation.

Clinical presentation and diagnosis:

Mild chronic hemolytic anemia exacerbates in the winter. Acrocyanosis and Raynauds phenomenon occur due to the agglutination of cells in the cooler vessels of the hands and feet. In few cases, a palpable spleen suggests a lymphoma or infectious mononucleosis. The paradox in CAD is the exacerbations that occur during febrile illnesses. This is because majority of the CAD patients have low levels of C3 and C4 during their steady states, due to continuous complement consumption. During acute phase reactions, the C3

and C4 levels increase due to their enhanced production, resulting in the exacerbation of hemolysis.

Diagnostic workup:

The first suspicion of CAD comes from the hematology laboratory's failed attempts to obtain a meaningful RBC count and indices. The RBC counts are decreased and MCV is falsely elevated, producing an unbelievably high MCHC, which can be rectified by prewarming the samples to 37ºC before feeding them into the analyzer. Patients may present with leucopenia and thrombocytopenia (due to presence of the I antigen on these cells).

Whenever cold agglutinins are picked up on peripheral smear, a cold agglutinin disease workup is advised which should include a reticulocyte count, bilirubin levels (which may be mildly elevated) and direct antiglobulin test which is generally positive with polyspeci f ic and ant i-compliment ant isera (C3d alone > C3d+IgG > IgG alone). A titre for the cold agglutinin antibodies may also be determined. In addition a serum protein electrophoresis with immunofixation electrophoresis is advised to rule out presence of paraproteins. If the patient is febrile and suspected to have interstitial pneumonia, a work up for Mycoplasma Pneumoniae and/or other viral markers may be required.

Take home message:

� In all CBC samples with MCHC >36, blood smear

should be examined to rule out red cell agglutination, and ideally the sample rerun after warming at 37°C for one hour

� CAD work up should include Reticulocyte count, Direct Coomb's test, serum protein electrophoresis

with IFE along with work up for other etiological factors based on clinical history and findings.



2014 Volume 27 No.110

Gut-specific Autoimmune Diseases

Dr. Philip Abraham, Dr. Abhijit Deshmukh & Dr. Meghraj IngleGastroenterology Department

Case History

A 27-year-old man with 3-month history of diarrhea with intermittent rectal bleeding was referred for evaluation. On examination, he had diffuse abdominal tenderness and no organomegaly. Laboratory investigations: hemoglobin 10.5 g/dL, ESR 45 mm in 1st hour, stools showed 20-25 WBC and 10-15 RBC/hpf, stool culture was negative.

Colonoscopy was done in view of the long history. It showed continuous inflammation and ulceration and friability from the anal verge up to 35 cm with a sharp cut-off, the mucosa above appeared normal, as did the terminal ileum. Histology of the biopsy specimen showed changes of chronic colitis with activity. TB culture was negative.

Discussion

Ulcerative colitis

Ulcerative colitis is an inflammatory bowel disease (IBD) characterized by abdominal pain and diarrhea with episodes of blood with the stools. Although it can start at any age, it usually affects people in the 20s and 30s. The disease affects only the mucosa of the large intestine, starting at the rectum and extending proximally for variable extents. Symptoms vary depending on the severity and extent of inflammation. Rectal disease usually presents with bleeding in stools and tenesmus. When the colon is involved, it presents with abdominal cramping and pain, and sometimes weight loss. The diagnosis is made on colonoscopy and histology.

The course of ulcerative colitis varies, with periods of acute illness usually alternating with remission. Fulminant colitis is a rare life-threatening form affecting the entire colon and causing severe pain, profuse bloody diarrhea and, sometimes, dehydration and shock; these patients are at risk of serious complications, including toxic megacolon and colon perforation. Other possible complications of ulcerative colitis include severe bleeding, anemia, extraintestinal manifestations (jaundice, arthritis, osteoporosis, episcleritis) and increased risk of colon cancer.

The goal of medical treatment is to control the inflammation and so prevent complications. Formulations of 5-aminosalicylic acid (5-ASA) like sulfasalazine, mesalamine, balsalazide and olsalazine are used as first-line therapy. These drugs can relieve symptoms in more than 90 percent of patients; those with only proctitis may be controlled with 5-ASA suppositories alone. Left-sided colitis may respond to mesalamine enemas, alone or in combination with the oral drug. Corticosteroids are used when this treatment fails. Immune-suppressor drugs like azathioprine are used as steroid-sparing agents, when the requirement for the latter exceeds safe limits. Cyclosporine is a potent drug that is reserved for those who have not responded to the other medications or may otherwise need surgery. Biologic agents such as infliximab are reserved for resistant cases. Surgery is curative for the colonic disease but carries its own morbidity.

Crohn's disease

Like ulcerative colitis, Crohn's disease is also an IBD, but marked by inflammation of all layers of the intestine. Depending on the region of involvement (in India, usually the ileo-cecal region or the large or small intestine, with normal mucosa alternating with affected segments), it presents with abdominal pain, diarrhea, fever and at times malnutrition and delayed growth or sexual development in children. Complications of this ulcerating disease include bowel obstruction, internal fistulae, rarely bleeding and anal fissures. Extraintestinal features include fatigue, arthritis, eye inflammation, skin disorders and hepatitis or cholangitis.

Blood tests usually show anemia and elevated C-reactive protein level. Colonoscopy might show ulcerated segments with skip areas in between. Histology often shows only non-specific changes of chronic inflammation but may show granulomas. The imaging and histology findings are almost identical to those of tuberculosis, to the extent that only culture for mycobacteria and / or a trial of anti-TB treatment may help to differentiate the two conditions. Other tests like barium studies, CT or MR enteroclysis, capsule enteroscopy or balloon enteroscopy are done to locate the disease and areas of stricture in the small bowel

2014 Volume 27 No.111

(capsule enteroscopy should be avoided when narrowing is suspected) and also to check for complications such as fistulae or abscesses.

Medical treatment begins with the use of mesalamine formulations. Corticosteroids are used in case of moderate to severe inflammation that does not respond to mesalamine. The corticosteroid budesonide has fewer side-effects and may be preferred in those with isolated ileo-cecal disease. Azathioprine is the most widely used immunosuppressant and may even be considered as first-line therapy, although the onset of action is slow and the drug is a weak suppressant. Infliximab and newer biologic agents (adalimumab, certolizumab) are indicated in adults and children with moderate to severe disease who do not respond to or cannot tolerate other treatments. Methotrexate and cyclosporine have been tried in patients not responding to the routine immunosuppresants and in whom the biologic agents cannot be used. It must be remembered that potent drugs (immune suppressants, biologics) carry risks of severe infections and malignancies on long-term use. Antibiotics like metronidazole and ciprofloxacin may help heal fistulae and abscesses. Surgery is generally kept as a last resort in patients with intractable disease with fistulae, abscesses and strictures not responding to optimal medical therapy. One principle of surgery is to be as conservative as possible; the chance of disease recurrence after surgery is quite high.

Celiac disease

Celiac disease is characterized by chronic inflammation of the small intestinal mucosa. There is a strong genetic predisposition, with major risk attributed to HLA-DQ2 and HLA-DQ8. Dietary proteins present in wheat, barley and rye, commonly known as glutens, interact with these HLA molecules to activate an abnormal mucosal immune response and induce tissue damage.

Clinical manifestations are highly variable, may present at any age, and involve multiple organ systems; prolonged delays in diagnosis are therefore common. Gastrointestinal manifestations may include diarrhea, vomiting, abdominal pain, bloating and distention, anorexia and constipation; weight loss or failure to grow are prominent features. It is common for Celiac disease to present with extraintestinal manifestations, sometimes with little or no gastrointestinal symptoms; examples include dermatitis herpetiformis, iron-deficiency anemia, unexplained short stature, delayed puberty, infertility, recurrent fetal loss, osteoporosis, vitamin deficiencies, fatigue, protein-calorie malnutrition, and elevated transaminases.

There is no one test that can definitively diagnose or exclude celiac disease in every individual. Characteristic lesions on small-intestinal biopsy include atrophy of villi, crypt hyperplasia, and increased intraepithelial lymphocytes. Serological tests like IgA antihuman tissue transglutaminase (tTG) and IgA endomysial antibody immunofluorescence (EMA) have high sensitivity and specificity. Two major endoscopic features are the disappearance or reduction of Kerckring folds and the scalloped configuration of reduced folds. These findings are however not specific.

Complications typically develop after many years of disease. These include refractory Celiac disease, ulcerative jejunoileitis, non-Hodgkin lymphoma, and enteropathy-associated T-cell lymphoma. The only proven treatment is strict and life-long adherence to a gluten-free diet. All foods and drugs that contain gluten from wheat, rye, barley and their derivatives must be eliminated. Treatment of vitamin and mineral deficiencies including iron, calcium, phosphorus, folate, B12, and fat-soluble vitamins should also be taken care of. Steroids and other immunosuppressive agents can be tried in refractory Celiac disease, i.e., those who do not respond to complete exclusion of gluten in the diet.

Autoimmune Pancreatitis (AIP)

Autoimmune pancreatitis (AIP) is a rare male-predominant disease occurring at median age of over 45 years. A common clinical presentation is recurrent acute pancreatitis or chronic pancreatitis, and rarely as a pancreatic mass. The disease may be accompanied by inflammation of the bile duct as well. AIP is known to be associated with inflammation of the salivary glands, retroperitoneal fibrosis, and tubulointerstitial nephritis.

AIP is now thought to be the pancreatic manifestation of a systemic disease called IgG4-associated systemic disease, which presents with unexplained fever, raised inflammatory markers, and fibrosis in and around organs. Pancreatic biopsy shows abundant lymphocytic and plasma cell infiltration, marked swirling (storiform) fibrosis, and obliterative phlebitis around the pancreatic duct. Immunohistochemical determination of IgG4-positive plasma cells is a useful adjunct to the serological (elevated IgG4 level) and histological diagnosis of AIP.

Although AIP is uniquely steroid-responsive, knowledge of the natural history and treatment of refractory disease is limited. Immune modulators like azathioprine and mycophenolate mofetil are used to reduce the steroid dose and side-effects.


2014 Volume 27 No.112

Autoimmune Hepatitis (AIH)

Patients with autoimmune hepatitis (AIH), usually middle-aged women, may present with non-specific symptoms such as lethargy, low fever, anorexia and nausea with accompanying jaundice, anemia and joint aches. Some may present like an acute hepatitis, and previous such episodes in history should raise the suspicion of AIH. The presence of associated autoimmune disorders including hemolytic anemia, thyroiditis, arthritis, ulcerative colitis, and the sicca syndrome adds to the possibility. Some patients may present in the late stage as cirrhosis with its complications.

Three main types have been identified. Type 1 is common in women between the ages of 15 and 40 while type 2 primarily affects young girls; type 3 affects children. The diagnosis is based on the presence of autoantibodies in the blood, like antinuclear antibodies (ANA), anti-smooth muscle antibody (ASMA) and anti-LKM1 antibody and by ruling out other common causes of chronic hepatitis. Liver biopsy not only confirms the diagnosis but also helps in determining the stage of the disease.

The mainstay of treatment is steroid, with most people needing to continue the drug for years and sometimes for life. Azathioprine is added to reduce the steroid dose. Management of late-stage disease is similar to that of cirrhosis of any etiology.

Primary Sclerosing Cholangitis (PSC)

Primary Sclerosing Cholangitis (PSC) is a chronic liver disease characterized by cholestasis, with inflammation and fibrosis of the intra- and extra-hepatic bile ducts. A large majority (75%-90%) of patients also have IBD; however, only approximately 4% of patients with IBD have or develop PSC. Two-thirds of patients are men, with mean age at diagnosis around 40 years. About a third of patients are asymptomatic and detected during screening of patients with ulcerative colitis who have elevated alkaline phosphatase levels.

Symptoms upon initial presentation include fatigue, jaundice, pruritus and right upper quadrant pain. Recurrent febrile episodes of bacterial cholangitis occur in 10%-15% of patients during the course of PSC. Cirrhosis, portal hypertension and liver failure are end-results of a progressive disease.

Liver function tests reveal raised alkaline phosphatase levels that are 3-5 times the reference range value. Serum aminotransferase levels are increased but not markedly so. Serum bilirubin level, predominantly the

conjugated component, is usually increased. Hypergammaglobulinemia is present in 30% of patients. Serum autoantibodies are detected in a majority of patients: antineutrophil cytoplasmic antibodies (ANCA) in 87%, anticardiolipin antibodies in 66%, ANA in 53%. These patients have an increased prevalence of HLA-B8, HLA-DR3, and HLA-Drw52a. ERCP was considered the gold standard for diagnosis; features include multiple strictures and dilatations of the intra- and extrahepatic biliary ducts. MRCP is now the preferred alternative. Liver biopsy is rarely required and shows concentric fibrosis with obliteration of the small ducts (obliterative fibrous cholangitis); this finding is virtually diagnostic but is found in fewer than 10% of biopsy specimens.

There is no curative medical therapy; the goals of medical management are to treat the symptoms and to prevent or treat the known complications. Therapies that have been tried include ursodeoxycholic acid (UDCA), which suppresses hepatic synthesis and secretion of cholesterol and inhibits intestinal absorption of cholesterol but also has a cytoprotective effect; this may lead to decreased cholestasis and improved liver functions. However, results are not satisfactory. Cholestyramine forms a nonabsorbable complex with bile acids in the intestine, which in turn inhibits enterohepatic reuptake of intestinal bile salts, reduces excess bile acids deposited in dermal tissue, and decreases pruritus. Antihistamines can also be used for pruritus. Immunosuppressive therapy has been tried with disappointing results. Balloon dilatation and stent placement can be done for blockages in the larger bile ducts. Liver transplantation is the only effective therapy and is indicated in end-stage liver disease.

Cholangiocarcinoma occurs in association with PSC in 6%-30% of patients. PSC is also a risk factor for colon cancer in patients with ulcerative colitis. The median length of survival from diagnosis to death or liver transplantation is 10-15 years.

Primary Biliary Cirrhosis (PBC)

Primary Biliary Cirrhosis (PBC) is a chronic and progressive cholestatic disease of the liver. The major pathology is destruction of the small and medium sized bile ducts, which leads to progressive cholestasis and often end-stage liver disease. Duct destruction is progressive, and is mediated by activated CD4 and CD8 lymphocytes. Subsequent to the loss of the intrahepatic bile ducts, a disruption of the normal bile flow occurs with retention and deposition of toxic substances that are normally excreted into bile.


2014 Volume 27 No.113

Frequently a disease of women, it occurs between the fourth and sixth decades of life; 25% are incidentally diagnosed during a routine blood evaluation. Fatigue is the first reported symptom. No correlation exists between this symptom and the stage of the liver disease. Pruritus is present in more than 50% of the patients, and 10% experience severe pruritus. Right upper quadrant discomfort occurs in 20% of patients. Physical examination may reveal jaundice, hyperpigmentation, xanthelasmata, xerophthalmia, xerostomia, features of the sicca syndrome, hepatomegaly and splenomegaly.

The hallmark of this disease is the presence of antimitochondrial antibodies (AMA), found in 90%-95% of patients, and they have a specificity of 98%. Significant elevations of serum alkaline phosphatase (ALP), Gamma-glutamyl transpeptidase (GGTP), and immunoglobulin levels (mainly immunoglobulin M) are the prominent lab abnormalities. Alanine a m i n o t r a n s f e r a s e ( A LT ) a n d a s p a r t a t e aminotransferase (AST) levels may be elevated. Hypercholesterolemia with high HDL levels are also found. The diagnosis is established or confirmed by liver biopsy, which reveals chronic, non-suppurative, destructive cholangitis of the small interlobular bile ducts, lymphocytic and plasma cell infiltration, with eosinophilic condensation in the portal tracts.

The goals of treatment are to slow the progression of the

disease and alleviate symptoms. UDCA is the major medication used to slow the progression especially early in the course of the disease. Immunosuppressants have been tried but with varying results. The agents used to treat pruritus are antihistamines, cholestyramine and colestipol, rifampin, and opioid agonists; pruritus is often refractory to medical therapy and significantly impacts quality of life. Plasmapheresis has also been tried for patients with severe pruritus intractable to medical treatment.

Compl ica t ions l i ke hypercho les te ro lemia, osteoporosis, renal tubular acidosis, and hepatocellular carcinoma can occur. Liver transplantation is the only life-saving procedure.

Gut-specific autoimmune diseases

Ulcerative colitis

Crohn's disease

Celiac disease

Autoimmune Pancreatitis (AIP)

Autoimmune Hepatitis (AIH)

Primary Sclerosing Cholangitis (PSC)

Primary Biliary Cirrhosis (PBC)


2014 Volume 27 No.114

Primary Autoimmune Neurological Disorders

Dr. Roopkumar GursahaniNeurology Department

Case History:

A 35 year old lady saw us for stumbling gait and a tendency to fall of 10 years duration. There was episodic fluctuation of her vision. Three months prior to the consult she developed upper respiratory infection and felt that her neurological disability worsened after that. She could not hold objects in her hands and complained of tremors and severe exhaustion. Since that time she had noticed pains on left and then right side of the body. Then, the patient abruptly developed a right hemisensory deficit after several days of work. The MRI scan was performed at that time and revealed a multifocal white matter disease - areas of increased T2 signal in both cerebral hemispheres. Spinal tap was also done which revealed the presence of oligoclonal bands in CSF. Visual evoked response testing was abnormal with slowed conduction in optic nerves. Gradually she developed weakness and numbness on the right side, impaired urinary bladder function and incontinence.

On examination: There was decreased hearing on the left, and numbness in the right face, which extended down into the entire right side. The Weber test revealed greater conductance to the right. Rinne's test revealed air greater than bone bilaterally. Tongue movements were slowed, but tongue power appeared to be intact. All the other cranial nerves were normal.

There was normal strength in the upper extremities throughout. However, rapid alternating movements were decreased in both upper extremities and the patient had dysdiadochokinesia in the left hand. Mild paraparesis was noted in both legs without severe spasticity. Deep tendon reflexes were +2 and symmetrical in the arms, +3 at the ankles and at the knees. Bilateral extensor toe sign were present. Sensory exam revealed paresthesia on the right to touch and decreased pin sensation on the right diffusely. The patient had mild vibratory sense loss in the distal lower extremities. Romberg's was negative. Tandem gait was mildly unstable.

Discussion

The above history is typical for a neurological condition

called multiple sclerosis. It belongs to a group of diseases which primarily affect the nervous system and have auto-immunity as its basis.

Multiple sclerosis (MS): It is a disabling neurological disease affecting the young and is regarded as an organ- specific inflammatory disease resulting from an aberrant immune attack on myelin or myelin-producing oligodendrocytes present in the central nervous system. Acute onset of focal neurological deficit may herald the onset of MS. Pathological hallmark of MS is the cerebral or spinal plaque, which consists of a discrete region of demyelination with relative preservation of axons. However, spectroscopic and pathological studies suggest some axonal loss may be an integral part of disease process. Histological examination of active plagues reveals perivascular infiltration of predominantly T lymphocytes and macrophages and occasionally plasma cells. Cranio-spinal MRI with contrast detects old and new plaques. CSF may be inflammatory in the acute stage. The back bone of t rea tment s t i l l remains s te ro ids . Var ious immunomodulatory agents including interferons, glatiramer acetate, alemtuzumab, mitoxantrone are often added to the regimen in case the disease is recalcitrant.

Other common/important autoimmune neurological diseases are:

Myasthenia Gravis: It is a disease of neuromuscular junction characterised by fatigable weakness of voluntary muscles. It is due to antibodies against postsynaptic muscle membrane. World wide prevalence is about 1/25000 population. It can occur throughout the life with, bimodal peak of incidence in younger women (second and third decade) and older men (in fifth and sixth decade). Common symptoms include easy fatigability, diplopia, dysphagia, dysarthria and dyspnea which are particularly worse after exercise and in the later part of the day, while the patient feels better after rest. Patients may present in acute myasthenic crisis with acute respiratory failure and may need ventilator support. Diagnostic tests done include neurophysicological tests like repetitive nerve stimulation, single fibre EMG (SFEMG) and blood tests

2014 Volume 27 No.115

l ike anti-acetylcholine receptor antibodies. Pyridostigmine, steroids, plasma exchange and immunoglobulins constitute various treatment options. In young patients, associated thymoma should be ruled out by doing a CT scan of the thorax.

Lamber Eaton Myasthenic Syndrome: This immunological disorder of nervous system is clinically similar to myasthenia gravis but antibodies are directed against presynaptic nerve terminal. The antibodies are directed against P/Q type voltage gated calcium channel present in nerve terminal. Diagnostic methods include the same battery of tests as mentioned in myasthenia gravis. This peculiar disorder often is associated with some malignancies, especially small cell lung cancer. Hence apart from confirming the diagnosis based on characteristic EMG/NCV pattern, effort must be made to rule out an underlying malignancy. Treatment include 3, 4 diaminophyridine with or without pyridostigmine along with the treatment of malignancy if detected. Plasma exchange and intravenous immunoglobulins are indicated in patients presenting in crisis.

Neuromyelitis optica (NMO): This peculiar neurological disorder is characterized by long segment cord demyelination with or without optic neuritis and demyelination in the brain. The definite prevalence is not known, but probably NMO is more common in eastern countries including India compared to the west. Presentation may be acute or subacute. The MRI changes are characteristic and detection of serum aquaporin 4 antibodies in the serum contributes to the confirmation of diagnosis. This antibody is IgG antibody binding to complement leading to conclusion that this is humoral disease in contrast to cellular immune mechanism proposed for multiple sclerosis. Treatment options include various types of immnunomodulations like intravenous steroid pulse, immunoglobulins and plasma exchange. Rituximab has been tried for prevention of relapse in anecdotal case reports.

Acute disseminated encephalomyelitis (ADEM): This is a monophasic demylinating illness characterised by multifocal CNS demyelination with encephalopathy as a prominent feature. Disease may start as a post infectious (most commonly measles) or post vaccination process. CSF is inflammatory with lymphocytic pleocytosis. Treatment options are usual immunomodulatory therapies.

Acute and Chronic Inflammatory demyelinating Polyneuropathies: Acute and chronic inflammatory demyelinating polyneuropthies (AIDP & CIDP) are autoimmune neurological disorders that cause progressiveness motor sensory weakness and a loss of sensation in the legs and arms. The pathogenesis is uncertain but molecular mimicry has been suggested. These disorders are diagnosed with electrophysiology studies showing slow nerve conduction velocities, variable velocities among nerves and prolonged latencies of F-waves. Treatment modalities in AIDP include intravenous immunoglobulins and plasma exchange. Patients with respiratory insufficiency may need ventilatory support. Treatment for CIDP consists of conticosteroids such as prednisolone and non-steroidal immunosuppressants such as cyclosporine A and methotrexate. When immunosuppressive treatments are inadequate, patients are treated with intravenous immunoglobulins and plasmapheresis.

Issacs syndrome: This disease in characterized by twitching, spasms and rippling of the muscles (myokymia) as a result of hyper excitablility of motor nerve fibers. Advanced cases manifest with generalized stiffness and weakness. Most cases are idiopathic, but a paraneoplastic variety is described where antibodies are found against voltage gated potassium channel. Few cases have been reported in association with polyneuropathy and thymoma. Phenytoin and carbamazepine abolish continous muscle fiber activity. Paraneoplastic variety responds to plasma exchange which, can be tried in resistant idiopathic varieties as well.

Stiff person syndrome: This condition is characterized by persistent and intense spasms particularly in proximal lower limbs and lumbar para-spinal muscles. Muscles of respiration and swallowing may be involved in advanced cases. About two third cases are associated with circulating autoantibodies to enzyme glutamic acid decarboxylase, an enzyme involved in synthesis of GABA. This condition is associated with other autoimmune disorders like pernicious anemia, thyroiditis and vitiligo. Diazepam is particularly useful in relieving the spasms while immunomodulation is useful for preventing recurrences.

Primary Autoimmune Neurological disorders

2014 Volume 27 No.116

Autoimmune Neurological Diseases

Acute and Chronic Inflammatory demyelinating Polyneuropathies

Issacs syndromeStiff person syndrome

Myasthenia Gravis Lamber Eaton Myasthenic Syndrome Neuromyelitis optica (NMO) Acute disseminated encephalomyelitis (ADEM)

Primary Autoimmune Neurological disorders

2014 Volume 27 No.117

Auto Immune Diseases & Ocular Manifestations

Ocular Pemphigoid

Autoimmune diseases are of two types: 1. Autoimmune diseases limited to eye. 2. Autoimmune diseases with systemic involvement.

It is not uncommon for an ophthalmologist to see a patient complaining of recurrent either painless or painful blurring of vision, redness or dryness of eyes. These symptoms can be manifestations of underlying autoimmune disease. Many a times these ocular symptoms can be associated with joint pains, dryness of mouth, skin lesions and sometimes these ocular symptoms are the only presenting symptoms. Such cases must be referred to clinicians for a systemic work up.

Recurrent ocular episodes, if left untreated can lead to visual disturbances or permanent ocular damage. These cases must be treated with a combined approach, of an ophthalmologist and a physician trained in immunology.

Ocular Pemphigoid

The patients usually present with redness, discomfort, grittiness and dryness in the eyes. The condition persists for many years with periods of spontaneous remission and flare-ups. Over a period of time there is scarring of the cornea with reduction of vision. There can be involvement of the mouth and skin as well.

Management includes local steroid drops to reduce inflammation and preservative free lubricants to keep the eyes moist. Systemic immunosuppresants may be

needed. Dapsone or a combination of steroid and cyclophosphamide are the first line of treatment. The treatment is continued till there is disease remission and then the drugs are gradually reduced and stopped.

Mooren's Ulcer

This is a rapidly progressive, extremely painful, ulcerative keratits which affects the peripheral cornea and spreads circumferentially and then centrally. It is not associated scleritis and there is no associated diagnosable systemic disorder detected. The cause is not known but this is an autoimmune disease directed against specific target molecule in the corneal stroma , probably triggered in genetically susceptible individuals. Clincially, there is peripheral ulceration involving superficial 1/3rd of cornea, progressive stromal thinning, vascularization of the stromal bed and scarring. Initially topical steroids, cyclopegics and prophylactic antibiotic are tried. If these fail, systemic immunosuppressive therapy is used. If all else fails surgical therapy like superficial lamellar keratectomy or penetrating keratoplasty is contemplatedespecially if there is perforation.

Peripheral Ulcerative Keratitis

This is characterized by severe, persistent peripheral corneal infiltration, ulceration or thinning unexplained by co-existent ocular disease. There is an underlying autoimmune disease due to which there is immune

Mooren's Ulcer

Dr. Nisheeta Agarwala, Dr. Prajakta SalunkheOphtalmology Department

2014 Volume 27 No.118


complex deposition in peripheral cornea. The auto antibodies may target sites in the corneal epithelium. Associated systemic diseases include rheumatoid arthritis, Wegener's granulomatosis, relapsing polychondritis and systemic lupus erythematosis. Treatment includes high dose systemic steroids and immunosuppresants. Keratoplasty is done either as an emergency in the event of a corneal perforation or electively to restore vision.

Episcleritis

Patient presents with acute onset redness and mild pain in one or both eyes, typically in young adults. History recurrent episodes is common. On examination there

is no discharge only sectoral redness of one or both eyes is seen with engorgement of episcleral vessels. These vessels are large and more radial in directions beneath the conjunctiva. If mild, episcleritis is treated with artificial tears qid. Moderate to severe episcleritis is treated with mild topical steroids.

Scleritis

This is a chronic, painful and potentially blinding inflammatory disease characterized by edema and

cellular infiltration of scleral and episcleral tissues. This can be infectious or associated with systemic autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, relapsing polychondritis, spondyloarthropathies, Wegener granulomatosis, polyarteritis nodosa and giant cell arteritis. It can be classified into anterior and posterior scleritis. Anterial scleritis - can be diffuse, nodular, necrotizing with inflammation and necrotizing without inflammation (scleromalacia perforans).

Posterior scleritis is characterized by flattening of the posterior aspect of the globe, thickening of the posterior coats of the eye and retro bulbar edema. Infectious scleritis requires appropriate treatment depending on the organism. Non infectious scleritis requires non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or immunomodulatory drugs. Rarely scleral grafts are required.

Uveitis

Uveitis (inflammation of the uveal tract) is an eye condition that can occur as an autoimmune disorder or as a result of injury, infection or exposure to toxins. It is classified into three groups:

(1) Anterior if it affects the anterior part of the uvea-the iris (Iridocyclitis)

(2) Intermediate if it affects the middle or vitreous get portion of the eye

(3) Posterior if it affects the retina and/or the choroids. The term "pan-uveitis" is used if all three compartments of the eye are affected.

The condition can be asymptomatic or present with modestly diminished vision that is slowly progressive, accompained with floaters. Vitritis is characterized by

Episcleritis

Scleritis


2014 Volume 27 No.119

Choroiditis

accumulation of inflammatory exudates in the form of snow-balls or snow-banks. It can result in vitreous degeneration or posterior vitreous detachment. Cataracts, especially the posterior sub-capsular variant, cystoid macular edema and in extreme cases, retinal neo-vascularization can occur.

Management includes local steroids, ocular injectable steroids and systemic steroids. In recalcitrant cases immunosuppressive medications may be required .

Birdshot Retino Choroidopathy

It is also known as vitiliginous choroiditis it affects females in the fourth to fifth decade of life. More than 90% of the patients are HLA-A29 positive. Symptoms include painless, gradual blurring of vision, floaters and loss of colour vision. Clinical signs multiple depigmented yellow-white patches which radiate from the optic nerve and follow the larger choroidal vessels. The term 'birdshot' is given because the pattern of the lesions in the fundus is similar to the shotgun scatter of a birdshot. Vitritis, optic disc edema and cystoid macular edema may be present. Ocular and systemic corticosteroids are used. It is usually a chronic disease with multiple recurrences and long-term visual prognosis is guarded.

Uveitis Birdshot Retino Choroidopathy

Vogt - Koyanagi Syndrome

Vogt-Koyanagi-Harada (VKH) disease is a multisystem disorder characterized by granulamatous panuveitis with exudative retinal detachment that is often associated with neurologic and cutaneous manifestations like poliosis, canities or vitiligo and neurological (meningo-encephalitis) disorders. It is treated with steroids and other immunosuppressive medications.

Autoimmune Retinopathy

Here, auto-antibodies directed at various retinal components cause progressive vision loss. Three forms of autoimmune retinopathy are known - cancer associated retinopathy, melanoma associated retinopathy and non neoplastic autoimmune retinopathy. These patients present with rapid, painless vision loss associated with photopsias and photosensitivity. This can progress to pan-retinal degene ra t ion w i t hou t p igmen t depos i t s . Corticosteroids - decrease antibody titers and stabilize vision. They usually cannot reverse vision loss. Plasmapheresis combined with steroids and intravenous immunoglobulin are also tried in severe cases. However treatment results have been very disappointing.


2014 Volume 27 No.120


Ocular Pemphigoid

Mooren's Ulcer


Episcleritis

Scleritis

Birdshot Retino Choroidopathy

Vogt - Koyanagi Syndrome

Autoimmune Retinopathy

Dry Eyes

Dry Eyes

Most of autoimmune diseases are associated with dryness of eyes and must be treated symptomatically

with preservative free artificial tear substitutes. Common complains of patient with dry eyes are pain, itching, redness of eyes blurring of vision, foreign body sensation and tearing episodes.

Don’t want to stay in the hospital too long !


2014 Volume 27 No.121

Autoimmune Diseases of the Skin

Dr. Nina Madnani Dermatology Department

Case History:

A 50 years old lady presented to the dermatology clinic with a six- year history of episodic symptomatic ulceration on the left buccal mucosa that would last for a few weeks, flaring up at times of stress. Range of motion of temporo-mantibular joint was limited by the right buccal mucosal scarring. She also complained of itchy violaceous rashes especially on the limbs. She was on treatment for hypertension and hypothyroidism since four years.

Intra-oral examination revealed multiple erosions and white streaks on the gingival and buccal mucosa. Pigmented areas were also found. There were violaceous polygonal flat-topped papules on the limbs. A clinical diagnosis of Lichen Planus was made and under local anesthesia a mucosal biopsy was performed, which was reported as "erosive lichen planus." The patient was treated with topical steroids. She was advised that local steroid injection could be considered, in the future, if necessary clinically

Discussion

Many skin diseases have an underlying autoimmune basis. In clinical practice, the commonest auto-immune skin diseases seen are lichen planus, alopecia areata, vitiligo, psoriasis, immune-bullous diseases, and chronic urticaria.

Lichen Planus

This is an autoimmune, papulosquamous disorder in which cytotoxic T-cells cause premature apoptosis of basal keratinocytes and destruction of basement membrane. It affects all age groups and involves the skin and mucous membranes. The skin lesions are characterized by itchy, violaceous papules which heal with intense post - inflammatory pigmentation. Oral disease may have varied morphological presentations but most patients complain of intolerance to spicy food. Erosive disease can be very painful and has an increased risk to malignant change, hence needs to be identified and treated early. Similarly, vaginal involvement may be seen, especially in older women, isolated, or as part of the vulvo-vaginal gingival

syndrome. The Hepatitis C virus has been associated with a significant risk of developing lichen planus. Topical corticosteroids are useful in limited disease. Antihistamines help to control the itch and tacrolimus is an alternative to steroids. Systemic treatment options include griseofulvin, metronidazole, acetretin, corticosteroids or rarely cyclosporine.

Alopecia Areata

Alopecia areata is an organ-specific auto-immune disorder postulated to be caused by an aberrant interaction between T-lymphocytes and HLA-DR antigens expressed by the keratinocytes of the hair follicles. Genes dictate the onset and severity of the disease. Children and young adults are commonly affected with an incidence between 10-30%. The individual develops asymptomatic coin shaped patch(es) of hair loss in one or more areas of the scalp, often first noticed by the hairdresser. The patches may increase rapidly to involve the entire scalp (Alopecia Totalis) or entire body (Alopecia Universalis). Other autoimmune diseases like thyroid disease, vitiligo, and inflammatory disease (Crohn's disease) may co-exist. Treatment is with intra-lesional / topical steroids, anthralin, tacrolimus, and/or topical 5% minoxidil solution for limited disease. Extensive disease may require topical immunotherapy, PUVA, or oral corticosteroids / methotrexate / azathioprine.

Vitiligo

This socially significant disease, is characterized by depigmented patches distributed over the body, occasionally in segmental or acral patterns. Vitiligo appears to be associated with certain alleles of the major histocompatibility complex (MHC) class II antigens as well as with other autoimmune-susceptibility genes. The positive response to immunosuppressive therapeutic agents emphasizes the role of autoimmunity in the development of this disorder. It is now considered a part of a broader autoimmune disease diathesis with an association with thyroid disease, alopecia areata, pernicious anemia, lichen sclerosis etc. There is a melanocyte-specific cytotoxic-T-cell immune reaction resulting in

2014 Volume 27 No.122

melanocyte destruction. Treatment modalities aim to generate pigment from melanin-containing appendageal structures like the hair follicles and also from the functioning epidermal melanocytes at the periphery of the patches. The extent and activity of the disease process dictates the type of treatment. All measures are aimed to convert an "unstable" disease to a "stable" one. Extensive disease may require oral steroids, NB-UVB, azathioprine, or methotrexate. Stable vitiligo can be treated with topical steroids, tacrolimus, anthralin and sometimes even surgery (esp. segmental variant). Lasers like the excimer laser, and targeted light therapy are the other modalities for small stable lesions.

Psoriasis

This is a chronic inflammatory skin disorder in which immunologically activated clonal T-cells stimulate basal cell proliferation in the epidermis. Typically, the disease presents as plaques with silvery scales on the bony prominences, but may involve the scalp, nails, or the entire integument. Patients have a strong association with HLA-Cw 6, HLA-Bw16, HLA-B13 and HLA-B17 and those with psoriatic arthritis, HLA-B27. Traditionally described as a disorder involving skin and joints, it is increasingly being identified as a systemic inflammatory disease affecting other systems particularly the cardiovascular system. Percentage of body surface area involved (> 10%) dictates the use of systemic drugs like methotraxate, cyclosporine or acetretin. PUVA, PUVA-SOL or NB-UVB is important for larger plaques. Topical treatments include high potency corticosteroids, tar-based ointments, calcipotriol and keratolytics. The importance of moisturizers can never be overstated. Biologicials like infliximab and etanercept are reserved for resistant cases, or those with joint involvement.

Immuno-bullous Disorders

This genetically determined group of disorders is characterized by circulating autoantibodies against cell membrane components or cell adhesion molecules. As a result, the skin splits at varying levels which gives the clinical phenotype.

Pemphigus Vulgaris (target: inter-cellular cementing substance) is seen in patients in their fifth decade, but may rarely be seen in a much younger age group. Circulating IgG antibodies are directed against cell adhesion molecules, (desmogleins -Dsg1 and Dsg3) within the epidermal keratinocytes resulting in their separation. Patients present with fluid-filled blisters on

the body and mucous membranes which easily rupture to leave behind large erosions. The disease can be effectively controlled with high dose corticosteroids and other immunosuppressants. Treatment may continue for years to maintain the disease in remission.

Bullous Pemphigoid (target: basement membrane) presents with tense bullae. The disease does not involve the mucous membranes and may not be as disabling as pemphigus vulgaris. Tetracycline and nicotinamide combination provide a good alternative to corticosteroids in controlling the disease. Potent topical corticosteroids are useful in limited disease.

Dermatitis Herpetiformis (target: dermo-epidermal junction) is associated with gluten sensitive en te ropathy. Mul t ip le smal l ves ic les are characteristically grouped on elbows, knees and buttocks. Severe itching is the hallmark of this disease as is the dramatic response to dapsone. A gluten free diet helps to reduced dapsone requirement if not control the disease.

Linear IgA Bullous diseases (target: dermo-epidermal junction) shows a bimodal peak. In children, the disease may start at 2-3yrs of age and spontaneously remit by the age of 13. The classical presentation is described as string of pearls since the bullae are arranged in a rosette or annular array. Dapsone helps to control the disease. The adult form of the disease is usually precipitated by drugs, most commonly - vancomycin and lithium.

Para-neoplastic pemphigus was originally described in patients presenting with oral erosions, and a b l i s t e r i n g d i s o r d e r w i t h a n u n d e r l y i n g lymphoproliferative malignancy. The histopathology was a combination of features overlapping between lichen planus and pemphigus. Now, besides l y m p h o p r o l i f e r a t i v e m a l i g n a n c i e s , l u n g malignancies, thymomas and sarcomas have seen to be associated. The diagnosis is a combination of clinical, histopathological, immunofluorescence findings, and the detection of an underlying malignancy. Patients demonstrate antibodies against desmoglein 3 and plakin proteins.

Chronic Autoimmune Urticaria

Chronic Autoimmune Urticaria (target: Fc receptors on mast cells, anti IgE antibodies) Around 50% of chronic idiopathic urticaria has now been identified to be autoimmune. Circulating IgG autoantibodies are


2014 Volume 27 No.123

directed towards the FcἐRI� receptors which are

present on the mast cells or rarely against IgE antibodies. Fusion results in degranulation of mast cells which in turn releases histamine and vasodilatory substances. A strong association with HLA-DR4 is seen in this group. Although thyroid autoantibodies may be positive, most of these patients may be clinically euthyroid. An important way to identify such patients is the Autologus Serum Skin Test (ASST). When antihistamines fail and patients are plagued with wheals and itching, immunotherapy with systemic corticosteroids, cyclosporine, or even plasmapheresis may be the only recourse.

Today, with new techniques of detecting autoimmunity, more and more traditional skin diseases are emerging as "autoimmune" diseases.

Lichen Planus

Alopecia Areata

Vitiligo

Psoriasis

Immuno-bullous Disorders

Autoimmune diseases of the skin

Chronic Autoimmune Urticaria

Vitiligo showing per-follicular re-pigmentation

Alopecia areata on beard area

Polygonal violaceous papules of lichen planus

o Pemphigus Vulgariso Bullous Pemphigoido Dermatitis Herpetiformiso Linear IgA Bullous diseaseso Paraneoplastic Pemphigus


2014 Volume 27 No.124

Adverse Effects of Immunosuppressive Therapy

Dr. Gurmeet Mangat

Although efficacious the various immunosuppressive agents have varied and important side- effects that one should be aware of while using them. This article highlights the important side- effects.

Corticosteroids

These are often the back bone of immunosuppressive therapy in various disorders. By nature steroids non-specifically suppress various arms of the immune system. The common side effects include weight gain, fluid retention, glucose intolerance and hypertension. However prolonged therapy also brings about a few important adverse effects like skin thinning, cushingoid features, osteoporosis, cataract and susceptibility to infections.

Hydroxychloroquine (HCQ)

HCQ is a mild immunosuppressive agent which acts on the immune system at an early stage of antigen presentation. It is used in rheumatoid arthritis and systemic lupus erythematosus. Common side-effects include itching and skin pigmentation on prolonged use. Rarely, it can cause pigmentary retinopathy. Hence all patients on hydroxychloroquine should have their fundus checked at least once a year. Myopathy and muscle weakness are the other extremely rare side-effects that can occur with prolonged use.

Methotrexate (MTX)

MTX has become the backbone of therapy for many auto-immune diseases especially rheumatoid arthritis. Usual side-effects include abdominal pain, oral ulcers and hair loss. These usually prevented to a large extent by the concomitant usage of folic acid.

Occasional elevation of transaminases (even up to 3 times the upper limit) is not uncommon and only needs temporary cessation of the drug. Persistent elevation of transaminases of more than 2 times the upper limit (6 episodes of elevation when measured every 6 weekly) usually necessitates stoppage of the drug. These patients also may merit liver biopsy. As the drug gets excreted by the kidney, its dosage should be reduced in those with renal involvement.

Extremely rarely it causes hypersensitivity pneumonitis. This usually presents sub-acutely (over a few weeks) with fever, cough and progressive dyspnoea. In such cases the drug needs to be stopped and patient started on high dose steroids to prevent morbidity and at times mortality.

Leflunomide (LEF)

LEF is a drug that is used mainly in rheumatoid arthritis and psoriatic arthritis. Its adverse effects mirror those of methotrexate. Liver and lung abnormalities, like that with MTX, are known with LEF. Loss of weight and peripheral neuropathy are other specific abnormalities known with LEF.

Azathioprine (AZA)

AZA has been used in rheumatic diseases like lupus for many decades. Apart from gastrointestinal side-effects it can cause cytopenia. This cytopenia is usually reversible once the drug is stopped. Rarely, it can cause drug induced hepatitis. Thiopurine methyltransferase (TPMT) is the main enzyme responsible for inactivating toxic products of azathioprine (AZA) metabolism. Patients with homozygous deficiency of this enzyme have no enzyme activity and ideally should not be given AZA as in them life threatening neutropenic sepsis occurs. This enzyme defect thankfully, is very rare. However, some recommend that all patients should be tested for TPMT activity prior to starting AZA therapy.

Cyclophosphamide (CPM)

CPM is a powerful immunosuppressant which has varied uses. It is generally reserved for organ threatening or life-threatening situations in patients with rheumatic diseases. It can be used in the oral or parentral form. Nausea and vomiting is not uncommon in the oral form. It can also cause leucopenia. Since its breakdown product acrolein is caustic, CPM causes haemorrhagic cystitis as acrolein dams up in the bladder. Intravenous CPM is less toxic than the oral formulation. Its tendency to cause cytopenia or haemorrhagic cystitis is much less than the oral formulations.

2014 Volume 27 No.125

Rheumatology Department

Cyclosporine

This drug acts through the calmoudulin pathway and affects the function of "T" cells. It is extensively used in organ transplant. In rheumatology it is mainly used in connective tissue diseases. Apart from gastro-intestinal side effects, it can cause elevated transaminases. Dose dependant hypertension and elevation of creatinine is also seen. Long term treatment can cause significant hirsuitism.

Mycofenolate mofetil

This new immunosuppressant is widely used in transplant setup and connective tissue diseases. The commonest side effect is abdominal pain and loose motions. It can also cause leucopenia.

Biological agents

Over the last decade target specific agents have been developed and used in rheumatology. The first group of drugs to be used was TNF-blockers (etanercept, infliximab and adalimumab). Subsequent to this various other biological agents have been produced.

Rituximab, Tocilizumab are some of them.

As a group they rarely cause major organ dysfunction as their side effects. Infections are the most dreaded complication since these agents suppress the immune system significantly (especially TNF blockers). In India, tuberculosis is an important worry and complication especially when using TNF blockers.

Corticosteroids

Hydroxychloroquine (HCQ)

Methotrexate (MTX)

Leflunomide (LEF)

Azathioprine (AZA)

Cyclophosphamide (CPM)

Cyclosporine

Mycofenolate mofetil

Immunosuppressive Agents

Adverse Effects of Immunosuppressive Therapy

2014 Volume 27 No.126

National Accreditation Board for Hospital & Health Providers

National Accreditation Board for Testing & Calibration Laboratories - Department of Laboratory Medicine

certificate: M -0620

Laboratory Tests In Rheumatology

Dr. Rohini Samant, Dr.Taral ParikhRheumatology Department

What tests do you really need to order for a patient?

1. A patient with possible rheumatic disease

2. A patient with known rheumatic disease

Primarily by history and physical examination

Increase your "pretest probability" by asking questions that support the diagnosis of

inflammatory arthropathy or systemic rheumatic d i s e a se.

Look for clues on physical examination.

Following routine tests may reveal helpful information in assessing a patient with possible rheumatological condition.

Anemia, other cytopenias - usually help inassessing the disease activity and in monitoring drug side effects. It is also necessary to be aware of other causes of changes in these parameters.

Dietary deficiency, autoimmune hemolytic anemia, NSAID induced GI blood loss, Felty's syndrome, drug induced marrow suppression, renal impairment

Low Hemoglobin Active rheumatoid arthritis (RA)

ESR Increased Acute phase reactants, anemia (fewer cells, less repellent forces)

CRP Direct measure of acute phase reactants.

Advantages - It is less sensitive to irrelevant factors like age, gender and anemia, responds more quickly.

Disadvantages - More expensive, don't always know how to interpret.

LOW: drug Induced marrow suppression, Felty's syndrome

HIGH: steroid therapy, acute arthritis, acute gouty attack, Still's disease

WBC abnormalities Low in active SLEHigh in infection and vasculitis

Platelet abnormalities Both disease related and unrelated

Systemic vasculitisDrug reaction Eosinophilia GPA, Granulomatous PolyAngiitis (GPA), PolyArteritis Nodosa

Eosinophilia

Thrombocytosis: Fe Deficiency, active RA, acute blood loss, vasculitis

Thrombocytopenia: Drug induced marrow suppression, APLA, Felty's syndrome, SLE

2014 Volume 27 No.127

Both ESR and CRP are not specific for any CTD, they help in drawing the attention towards the systemic inflammatory response versus a more benign condition. In most of the diseases a decrease in these parameters usually suggest a response to therapy.

Urinary abnormalities- like active urinary sediment helps in diagnosing renal involvement in conditions like SLE and systemic vasculitis.

Elevated serum creatinine is a marker for diagnosing rapidly progressive cresentric GN and underlies the need for a more intensive therapy I ncluding kidney biopsy.

CPK elevations are associated inflammatory myositis.

High globulins suggest an active disease and a chronic inflammatory state.

Liver function tests helps in detecting the liver involvement in various diseases and in monitoring side effects of immunosuppressant therapy.

Thyroid function tests should be ordered as it is a common cause for various musculoskeletal complaints and its prompt treatment alleviates many of these complaints.

Vitamin D3: If the patient is affording this test should be ordered. Vitamin D3 supplements may be given without testing if the patient is not affording as in India Vitamin D3 deficiency is very common, more so in rheumatic diseases.

Chest X ray as a part of routine investigation is helpful not only for diagnosing underlying ILD in various CTDs but also in ruling out infections such as tuberculosis.

Common Immunological Tests

Screening Tests

These tests are ordered when a patient has history and

Rheumatoid factor is not diagnostic for rheumatoid arthritis. The test's utility is greatest when there is a moderate pre-test probability of the disease.

Anti-CCP antibody - it is newer test for diagnosing RA. It is an antibody directed against "c i t ru l l ina ted" pept ide res idues present within inflammatory sites. It has a sensitivity equivalent to RF and greater specificity than IgM RF. It is part of the new 2010 ACR guidelines for diagnosis of RA. It may be detected in healthy people years before onset of RA.

ANA (Anti nuclear antibody) - It is the most important screening test for a connective tissue disorder (CTD), like SLE in a patient presenting with features like fever, hair loss, photosensitive rash, mouth ulcers and arthritis. Its absence virtually excludes SLE and it is positive in 95% of S L E cases.

It is also positive in other CTDs like Scleroderma and Sjogren's syndrome.

Non rheumatological conditions with RF positive

o Viral infections - Hepatitis C o Parasitic infections - Kala Azaro Chronic bacterial infections - T.B, Hansen'so Neoplasm

symptoms suggestive of an underlying rheumatic condition.

Rheumatoid Factor (RF) - It is the most commonly used screening test for diagnosis of inflammatory polyarthritis (RA). It is positive in other conditions like- MCTD, SLE, Scleroderma, Sjogren's syndrome, Cryoglobulinaemia.

It is positive in 75% of RA patients and associated with extra articular manifestations. But in may be present in 15% of population > 65 years of age.

Malignancies: lymphoma, leukemia, melanoma, solid tumors (ovary, breast, lung, kidney)

Non - rheumatological conditions with positive ANA

Normal individuals: females > males, increasing age, relatives of patients with rheumatic disease, pregnancy

Autoimmune thyroiditis, Type 1 Diabetes Mellitus

Hepatic diseases e.g. chronic active hepatitis

Pulmonary diseases e.g. idiopathic pulmonary fibrosis

Chronic infections

Hematologic disorders: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia

Drug- induced: hydralazine, phenytoin


2014 Volume 27 No.128

So, when should I order an ANA?

o Perinuclear staining - P-ANCA

o Cytoplasmic staining -C-ANCA

But it is not required to confirm a clinical and radiologic diagnosis of Ankylosing spondylitis (AS). Its sensitivity is 95% for patients with Ankylosing spondylitis, 70% with reactive arthritis, and 60% with Psoriatic spondylitis (PSA).

It is important to keep in mind that it is present in 5-8% general population. HLA B27 of no value in diagnosing usual patient with back pain.

Uric acid

It is a commonly abused test. Before ordering this test it

is important to keep in mind the clinical profile of patient with gout- monoarticular, acute involvement of MTP joint typical of gout, but acute knee, ankle or polyarticular involvement may occur.

Asymptomatic hyperuricemia is a common component of the metabolic syndrome and only a small proportion of patients with asymptomatic hyperuricemia will develop gout. It is important to know that the incidence of gout increases as the severity and duration of hyperuricemia increases.

Synovial fluid analysis

It is important for diagnosing infectious arthritis, crystallopathies like gout and CPPD (Calcium Pyro Phosphate Deposition) and monoarthritis.

Infections usually cause a synovial fluid WBC count > 50,000 c/mm3, inflammatory arthritis and crystallopathies WBC count between 5,000-50,000 c/mm3 and non inflammatory conditions like OA have a WBC count < 500/mm3.

Imaging Techniques in Rheumatology

a)Plain X-ray hands with wrists help in diagnosing various conditions like RA, SpA, gout and assessing the presence of damage like erosions and joint space narrowing.

Plain X-ray SI joint for diagnosing SpA like AS, PsA and x- ray lumbar and cervical spine for involvement in RA and SpA.b) CT scan and MRI

c) Ultrasound is gaining popularity for diagnosing inflammatory arthritis, shoulder disorders and for joint aspiration and injection.

d) Radioisotope scanning is not ordered as a routine test and in unusual situations it is helpful in picking up an occult inflammatory arthritis or infection.

Tests for extra articular manifestations


2014 Volume 27 No.129

ANCA most strongly associated with necrotizing vasculitis

C-ANCA (Pr3) Wegener's granulomatosis / Granulomatous polyangitis

P-ANCA (MPO) Microscopic polyangitis, Churg-Strauss vasculitis

background illness.These tests are important for assessing the systemic involvement in CTD like the lungs, heart, kidney and brain. Following are some of these tests:X-ray Chest (effusion, nodules, infections), PFT (DLCO), CT-Chest (HRCT), BAL: for pulmonary involvement.

CSF, MRI, and CT-Brain: for CNS involvement.

2 D Echo for PAH and cardiac involvement in CTDs.

Barium Studies, OGD scopy - Scleroderma

EMG, nerve Conduction- in peripheral neuropathies and myositis.

Bone Densitometry - DEXA, T Score, Z score; osteoporosis.

Other tests

HBsAg, Anti HCV, TSH, lipid profile, serum electrophoresis, VDRL, HIV, Hb electrophoresis, cryoglobulins, immunoglobulins, anti phospholipid antibodies dictated by the patients history and


2014 Volume 27 No.130

Role of CT Scan Early diagnosis of sacroilitis, vertebral disease and d e s t r u c t i o n , subchondral fractures

Role of MRI scan Most sensitive for avascular necrosis, craniocervical region in RA, SpA, direct v isual izat ion of articular cartilage

Auto antibodies are the markers of future disease in

presently healthy individuals. Although auto antibodies

might not always be directly responsible for many of the

manifestations of auto immune diseases, but assaying

auto antibodies for prediction of disease could lead to

intervention trials to prevent auto immune organ

specific diseases like Type 1 Diabetes, Thyroid disease,

Myasthenia gravis or systemic illnesses like Rheumatoid

Arthritis (RA) and Systemic Lupus Erythematosus

(SLE).Thus predictive auto antibodies are molecules

that appear in blood years before people show

symptoms of various disorders. Tests that detect these

molecules could warn of the need to take preventive

action.

Auto Antibodies as Markers of Disease Activity,

Severity and Classification

Antibodies may reflect the presence, nature and

intensity of immune response. Since in auto immune

diseases the immune response is itself part of the

disease process, it is possible to use auto antibodies as

markers of disease activity. These auto antibodies can

be detected in certain diseases with a long prodrome

during which there are no clinical symptoms. The titer or

the levels of these auto antibodies can also predict both

the likehood of clinical disease and rate of progression

of the disease i.e. the disease activity and the severity of

the disease.

Many auto immune diseases are chronic condition that

progress over the course of time and are characterized

by the presence of auto antibodies that precede the

overt disease by months or years. It is now known that

the presence of two, Islet cell Antibodies (ICA) are

associated with a 50% risk of developing diabetes

mellitus in 5 years, Anti Cyclic Citrullinated Peptide

(Anti-CCP) antibodies are found in sera of Rheumatoid

arthritis patients 4 to 5 years before the overt disease,

and in SLE patients accrue antibodies throughout a

foreseen course during 3 - 4 years before the clinical

symptoms.

The introduction of tests recognising Anti CCP

ant ibodies has revolut ionised pract ice in

Rheumatology. These antibodies have recently

emerged as sensitive and specific serological markers

of Rheumatoid Arthritis (RA), providing an additional

and superior marker of rheumatoid factor. The first

members of this autoantibody family were anti-

perinuclear factor and anti-keratin antibodies both of

these recognise citrullinated epitopes of flaggrin.

Citrullination is a post translational modification of

arginine by deimination, physiologically occurring

during apotosis, inflammation or keratinization. The

presence of several citrullinated proteins has been

demonstrated in RA synovium. The identification of

citrullinated epitopes as targets for antiflaggrin

antibodies led to the development of first and later

second generation anti-cyclic citrullinated peptide

antibody assay.

With the availability of sensitive and specific assays, Anti

- CCP antibodies has become a "Key" serologic marker

in RA and is considered a potential surrogate marker for

diagnosis and prognosis of rheumatoid arthritis. It is

now included in the classification and diagnostic

criteria of American College of Rheumatology.

a) Since it is more specific than IgM rheumatoid

factor (RF)in early and fully established disease

b) Can predict eventual development into RA when

detected in undifferentiated arthritis.

c) A marker of erosive disease in RA.

d) May be detected in healthy individuals' years

before the onset of clinical RA.

It remains to be seen whether the use of Anti - CCP

antibodies will allow the clinical rheumatologist to

better predict the diagnosis and prognosis of individual

patients and help in more rational therapeutic decision

making thus influencing the long term outcome of the

disease. Although screening of populations for

susceptibility to certain autoimmune diseases is now

feasible, high throughput, cost effective methods

should be available to detect individuals at high risk for

a specific autoimmune disease. The practical value of

screening will be enhanced once preventive measures

and safe therapy become available.

On the trail of diseases, years before they strike - Auto antibodies

Dr. Vipla PuriRIA Laboratory Department

2014 Volume 27 No.131

Rheumatology Quiz

What is your diagnosis?What test will prove it?

Q1 : 40 yrs old male with back pain of

10 years duration

Q 3: A 60 years old man with painful

right lower limb

What is the diagnosis?What other tests will you do?What is the treatment of choice?

Q 2: A 12 years old boy with pain in

the legs

What does the plain x-ray show?What is most likely disease? What is the diagnosis?

Q 4: 43 years old male with easy

fractures

Q1: 1) Alkaptonuria 2) Urinary homogentisic acid Q2: 1) Subcutaneous calcification 2) DermatomyositisQ3: 1) Paget’s disease of the tibia 2) serum alkaline phosphatase, urinary collagen cross links, bone scan 3) If active: BisphosphonatesQ4: Interrosseous membrane calcification due to fluorosis.

Answ

ers

2014 Volume 27 No.132

Dr. C. Balakrishnan

Our Team

Dr. V. R. JoshiM.D., FRCP

Consultant Physician & RheumatologistDirector, Research

Dr. C. BalakrishnanMD

Consultant Rheumatologist

Dr. Rohini SamantMD


Dr. Gurmeet MangatMD


Rheumatology Faculty

2014 Volume 27 No.133

P. D. Hinduja Hospital & MedicalResearch Centre - News

2014 Volume 27 No.134

P. D. Hinduja Hospital retains position of the Best Multi-Specialty

Hospital in MumbaiTitle bestowed at the first edition of Healthcare Achievers Awards 2014

P. D. Hinduja National Hospital & Medical Research Center, Mumbai continues this year's award-winning streak with the prestigious title of the 'Best Multi-Speciality Hospital-Mumbai' (survey-based category) awarded at the Healthcare Achievers Award 2014, presented by New India Assurance Co. Ltd. and The Times of India on 11th December 2014 in New Delhi. In its first year, the awards have been instituted to honour excellence in the Healthcare Sector across single speciality, multi-speciality and secondary care hospitals, who have contributed in helping India emerge as one of world class destinations in healthcare. This recognition re-affirms Hinduja Hospital's position asa pioneer and leader in health care delivery in the country.

In an evening that celebrated excellence in Healthcare, P. D. Hinduja Hospital was recognized

as the healthcare provider who raised the bar for this industry with its dynamic spirit and innovative outlook thereby helping people lead quality lives. The award was presented by Union Food and Consumer Affairs Minister, Ram Vilas Paswan to the hospital Trustee Mrs. Usha Raheja, along with Mr. Gautam Khanna, CEO, Mr. Joy Chakraborty, COO and Dr. Sanjay Agarwala -Director of Professional Services, ofP. D. Hinduja Hospital, at the event that witnessed leaders from across the pharmaceutical and healthcare industry. Shri G. Srinivasan, Chairman & Managing Director of The New India Assurance Co. Ltd, Mr. Luv Verma, Secretary-Dept. of Health and Family Welfare and Mr. Joy Chakraborthy, Director Times Of India group were among the dignitaries present at the event.

The consistent recognition gained by P. D. Hinduja Hospital this year, showcases the trust shown by patients and communities in the core values of the institute and the quality of care provided by the hospital. Speaking on the occasion, Managing Trustee Ms. Vinoo S. Hinduja said, "We have always stood by our mission of 'Quality Healthcare' with a strong sense of purpose laid by the founder of the hospital, Sri Parmanand Hinduja, to serve our patients. The consistency, with which P. D. Hinduja Hospital has been recognized as one of the country's best hospitals, reflects the growth, hard work and dedication to patient-centered care and excellence that is embedded in our legacy. Through innovative technology, accreditation and knowledge driven employees, our hospital has been relentless in its pursuit of excellence."

The winners of the 'Best Multi-Speciality Hospital in Mumbai' - at the first edition of Healthcare Achievers Awards 2014, were determined through a research

'Best Multi-Speciality Hospital-Mumbai' (survey-based category) awarded at the Healthcare Achievers Award 2014, presented by New India Assurance Co. Ltd. and The Times of India

From Left to Right: Mr. Joy Chakraborthy, Director - Times Group, Mr. Gautam Khanna, CEO-P.D. Hinduja Hospital & MRC, Mrs. Usha Raheja, Trustee-P.D. Hinduja Hospital & MRC, Shri Ram Vilas Paswan, Union Food and Consumer Affairs Minister, Mr. Luv Verma, Secretary-Dept. of Health and Family Welfare, Mr. Joy Chakraborty, COO-P. D. Hinduja Hospital & MRC, Mr. G. Srinivas, CMD-The New India Assurance Co. Ltd, Dr. Sanjay Agarwala, Director-Professional Services, - P. D. Hinduja Hospital & MRC

2014 Volume 27 No.135

th26 January, 2014 workshop

Contd.

methodology based on factual information obtained from numerous short listed hospitals across India. The survey included feedback from the doctor community towards understanding the hospitals in their consideration and preference list. Patients evaluated the hospitals based on behavioral and emotive loyalty besides their performance based on "Compassionate patient care", "Patient safety" and "Customer excellence"

"We are extremely proud and honored that our continued dedication and passion for providing high quality care to each and every one of our patients was recognized by these prestigious awards. We are constantly investing in technology and talent to ensure we operate to the highest possible standard and continually provide newer solutions and care for patients." said Mr. Gautam Khanna, Chief Executive Officer, P. D. Hinduja Hospital.

P. D. Hinduja Hospital has provided more than six decades of selfless and dedicated service of providing ethical, value based quality healthcare for the people of India. The hospital has recently received various industry awards for healthcare delivery, innovation and technology. The institution's focus has always been to provide a patient centric healthcare experience that allows access to the best doctors and technology at an affordable cost.

P. D. Hinduja Hospital & Medical Research Centre to cement an Innovation Lab

P. D. Hinduja Hospital, IIT-Bombay, WeSchool come together to create a platform

for innovation for the youth of India

thOn occasion of the 65 Republic Day of India when India looks at becoming a young superpower, this event created a

platform for innovation and opportunity for the youth of India. The event is the beginning of a week-long workshop

being held at IIT Bombay and at WeSchool with MIT delegates.

During this event, doctors from P. D. Hinduja Hospital presented their innovative ideas and expectations to the young

and entrepreneurial students from IIT-B, WeSchool and MIT.

Inspired by the doctors wish list, P. D. Hinduja Hospital's Executive Trustee Ms. Vinoo Hinduja announced an

"Innovation Lab" where the youth of India would come together to develop economical medical and diagnostics

equipments/facilities for the people of India. This Innovation Lab will be 'By India, Of India and For India' and Indian

institutes like IIT-B and WeSchool will join hands with P. D. Hinduja Hospital to create this platform with MIT being

facilitator in this innovation. P. D. Hinduja Hospital looks forward to many more collaborations with domestic and

international institutes for its innovation lab.

P. D. Hinduja News

Announcing the new innovation lab, Ms. Vinoo Hinduja said, "The deficiencies in healthcare industry are a fertile land

waiting for the youth of India to plant it seeds of innovation to reap the fruits of success. I urge you all to embrace

transformation so as to be able to address some of patient care issues."

Mr. Joy Chakraborty, COO, P. D. Hinduja Hospital said, "India needs innovation to make healthcare accessible and

affordable. Our endeavor is a small step towards the need of the health sector. One of our principles 'Partnership for

Growth' is followed in different ways in our practices and this Innovation Lab will stand for a partnership with credible

and similar minded partners across the globe to achieve our objectives."

Dr. Sanjay Agarwala, Director - Professional Services said, "This is a forum where all participating students from IIT,

MIT etc could interact with doctors of Hinduja Hospital so that they could innovate and find solutions through ideation,

leading to a product that would help the same doctors across the world in diagnosis."

The P. D. Hinduja Hospital has always been in the forefront of technology. Dr. Camilla Rodrigues, Consultant

Microbiologist & Chairperson Infection Control Committee said, "One of the thrust areas has been in tuberculosis

diagnostics. The hospital is well known as a pioneer in this field. The Govt of India has recently recognized our lab for

second line testing of drug resistant tuberculosis. This innovation lab initiative that will also focus on TB is certainly a

step in the right direction to the laudable goal of a TB free India.”

Contd.

P. D. Hinduja Research Centre and Hospital celebrated Republic Day by felicitating th50+ Organ Donors to spread awareness for Organ Donation on 26 January, 2014

~Film maker Madhur Bhandarkar aralong with Director Karan Malhotra, Actor Darshan Jariwala & well

known Comedian Manoj Joshi were a part of the awareness programme at the hospital~

~Cardiac patient father who donated kidney to daughter suffering from Juvenile Diabetes, Donor from Nagaland

amongst others were felicitated~

Pioneering healthcare provider-P. D. Hinduja Hospital has pulled out all the stops to take healthcare a step further by th

felicitating the heroic act of organ donation. In its 7 edition, the organ donor felicitation endeavour anchored by the

hospital aims at honouring & encouraging donors from various walks of life for their noble act. National Award-

winning film maker Madhur Bhandarkar along with new age Director Karan Malhotra (of Agneepath fame),

National Award winning actor Darshan Jariwala

and well known character artist & comedian Manoj

Joshi were seen applauding the spirit of 50+

national & international donors who were

felicitated on the occasion of Republic Day at

Hinduja Hospital.

Speaking on the occasion Dr. Alan Almeida,

Section Co-ordinator, Nephrology says, 'For

organ recipients, a transplant often means a second

chance at life & allows many recipients to return to a

normal lifestyle. We at Hinduja Hospital strongly

advocate the cause of organ donation and ensure

the process is fruitful for each recipient. Our efforts

are concentrated to bridge the demand supply gap

of organs in the country as about 5,00,000 people

die to non-availability of organs every year’

Dr. M. Kamath & Film maker Madhur Bhandarkar applauding the spirit of the donors at the Organ Donation Felicitation

programme by Hinduja Hospital

2014 Volume 27 No.136

P. D. Hinduja News

P. D. Hinduja Research Centre and Hospital's Allied Health Sciences Courses gets

HSSC affiliation

The Allied Health Sciences Courses which got off to a flying start since its launch in 2012 has now received an affiliation from the Health Sector Skills Council (HSSC), a not-for-profit organization, registered under the Societies Registration Act, 1860. The affiliation from the council makes Hinduja Hospital the only hospital in the country to have been certified to conduct these allied courses under pilot phase of Star Scheme of Government of India. The council has been promoted by Confederation of Indian Industry (CII) and leading Healthcare Industry Members representing both public and private sector, constituted and financially supported by National Skills Development Corporation (NSDC a pioneering PPP set up under the aegis of Ministry of Finance). P. D. Hinduja Hospital will be conducting courses in 4 primary departments namely Radiology, Dialysis, Medical Laboratory and Operation Theater.

The courses are being conducted in 2 formats: Part-time & Full time. The Part-time course begins from January and caters to the practicing professionals who are HSC pass and have experience in the field. Duration of course is 7-months, with once a week lectures. The same courses are also available as full time with duration of 1 year, catering to freshers, whose batches will start in August 2014. Other full time courses (non-affiliated) from the Allied Health Sciences stable are MRD Technician, CSSD Technician and Physician office assistant courses. These courses will be beneficial to the students by giving them the opportunity to get certified under government scheme along with enjoying get monetary reward on certification.

2014 Volume 27 No.137

P. D. Hinduja Hospital & Medical Research Centre, established in 1951, a leading tertiary care hospital in India, has been adjudged as the 'Best Multi Specialty Hospital of The year' at the e-Health Maharashtra Healthcare Leadership Awards & Summit held on July 11, 2014. At a glittering ceremony held at The Courtyard Marriott, Pune, Mrs. Meeta Rajiv Lochan, Secretary, Department of Public Health, Govt. of Maharashtra presented the award. Mr. Joy Chakraborty, COO, P. D. Hinduja Hospital received the award on behalf of the Hospital.

Mr. Gautam Khanna, CEO, P. D. Hinduja Hospital said, “We feel proud to be adjudged as the best multi specialty hospital and to have received this prestigious award. It was our

Founder, Sri. P. D. Hinduja's vision to build a world-class, affordable hospital to provide Quality Healthcare for all at par with international standards. The dream was then later carried forward to reality by Late Smt. Lalita G. Hinduja,Sri. P. D. Hinduja's eldest daughter-in-law, who spent 30 years nurturing this vision. She created a culture of compassion and care amongst the employees, weaving them into a family. Mr. Khanna added, “It is the patient centricity and parivaar values at the Hospital which make employees go beyond the call of duty to deliver high quality, affordable, personalized care to all patients.”

Mr. Joy Chakraborty, COO, P. D. Hinduja Hospital on receiving the award said, "We are extremely delighted to have received this award. The recognition is a result of the commitment of every individual working with the hospital in giving the best patient care. This award will be a great motivation for the staff at the hospital.” He attributed the achievement to the strong sense of purpose laid by the Founder of the Hospital, Sri Parmanand Hinduja, to serve the community.

The hospital had won the e-Maharashtra award for the 'Best ICT enabled hospital' in 2013. The current award in 2014 is another stepping stone in the relentless pursuit of excellence for the Hospital.

P. D. Hinduja Hospital adjudged as “Best Multi-Speciality Hospital of the

Year” at e-Health Maharashtra Awards 2014

P. D. Hinduja News

Welcome to P. D. Hinduja Hospital Pariwar

Dr. Aman Daftary Imaging (Mammography

and Breast MRI)MBBS, DMRD

Dr. Ameet Mandot Gastroenterology

Visiting Consultant MBBS, MD, DNB (Gastro)

Dr. Purushottam Kand Nuclear Medicine

M.B.,B.S.(Mum), D.R.M.(Mum),

D.N.B.(Nucl. Med.), M.N.A.M.S., Diplomate C.B.N.C.(USA)Fellow, European Board of

Nuclear Medicine

Dr. Nilesh Doctor Gastroenterology Visiting ConsultantMBBS and FRCS

Dr. Ganesh Nagarajan Gastroenterology Surgery

(Oncology)M.S, FCPS,

Fellowship HPB & Liver Transplant (France)

Dr. Neelu Desai Pediatric Neurology

MD (Ped), DNB, Bill Marshall Fellowship (UK),

Fellowship in Pediatric Neurology (London)

Dr. Lancelot Pinto Pulmonology

MBBS, DNB (Respiratory Medicine), MSc (Epidemiology - McGill

University, Canada), Fellow (Sleep medicine and COPD

Rehabilitation - McGill University, Canada),

FCCP (USA)

2014 Volume 27 No.138

Dr. B. Satyanand Shastri Pulmonology MBBs, MS,

FRCS.

Dr. Raashi Khatri Panjabi MD (USA), BDS

Visiting Consultant in Orofacial Pain Management including

Temperomandibular Disorder, Post Cancer Jaw Stabilization, and

Musculoskeletal pain & Neuropathies of head & neck

Spreading health & happiness

as we move ahead!

by Doc N Doc ‐ Gammex Saviour Awards. We believe it is your faith in us that has been our biggest motivation in being the best!

,

Awarded

N E W S L E T T E R - Hinduja Hospital...Dr. Kunal Sehgal, Dr. Neha Lankhe Hematology Department Let...

Documents

Transcript of N E W S L E T T E R - Hinduja Hospital...Dr. Kunal Sehgal, Dr. Neha Lankhe Hematology Department Let...