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CASE REPORT
Year : 2007  |  Volume : 61  |  Issue : 7  |  Page : 414-417
 

Celiac disease: Association with adult-onset Still's disease: Apropos of a clinical case


Department of Medicine, Maulana Azad Medical College and Associated Lok Nayak and G. B. Pant Hospitals, New Delhi, India

Correspondence Address:
Sachin Kumar
E 27, Vikram Nagar, Firoz Shah Kotla, New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5359.33191

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 ¤ Abstract 

Adult-onset Still's disease (AOSD) is a rheumatic disorder of unknown etiology characterized by a triad of fever, polyarthritis and evanescent rash. We present a case report of a 28-year-old female who presented with complaints of fever, joint pains, rash, weakness for the past 4 years and diarrhea for the past 2 years. On investigation the patient was diagnosed to be a case of AOSD. Duodenal biopsy report was suggestive of celiac disease with a positive IgA tissue transglutaminase and anti-endomysial antibody. The patient was started on weekly methotrexate and gluten-free diet, and her symptoms gradually improved. The patient remains in our follow-up and is doing well.


Keywords: Adult-onset Still′s disease, autoimmune diseases, methotrexate


How to cite this article:
Kumar S, Gupta N, Jhamb R, Mishra D. Celiac disease: Association with adult-onset Still's disease: Apropos of a clinical case. Indian J Med Sci 2007;61:414-7

How to cite this URL:
Kumar S, Gupta N, Jhamb R, Mishra D. Celiac disease: Association with adult-onset Still's disease: Apropos of a clinical case. Indian J Med Sci [serial online] 2007 [cited 2015 May 27];61:414-7. Available from: http://www.indianjmedsci.org/text.asp?2007/61/7/414/33191



 ¤ Introduction Top


Adult-onset Still's disease (AOSD) is a multisystem inflammatory disorder characterized by high spiking fevers, evanescent salmon-colored rash, arthralgias or arthritis. AOSD is quite uncommon in occurrence, with an estimated prevalence among those aged 16 years or older of 0.73 and 1.47 per 100,000 population for males and females respectively. [1] There have been isolated case reports of AOSD in association with thrombotic microangiopathy and juvenile rheumatoid arthritis with celiac disease. [2],[3] To the best of our knowledge, till date this is the first case report mentioning the association of AOSD with celiac disease. The case highlights autoimmunity as the common denominator for this rare occurrence, which is further strengthened by genetic polymorphisms within the human IL18, found both in AOSD and celiac disease patients.


 ¤ Case Report Top


A 28-year-old female presented with complaints of fever, joint pain, rash, generalized weakness for the past 4 years and diarrhea for the past 2 years. The fever was moderate to high grade (>39.3°C) in intensity and was associated with evanescent erythematous rash, predominantly involving the trunks. The joint pain started in the right wrist and within a month it progressed to involve the other wrist joint, small joints of hands and bilateral knees. There was no history of trauma, chest pain, breathlessness, urethritis, conjunctivitis. At the time of presentation, she had severe symmetrical nonmigratory polyarticular arthritis.

Two years later, the patient developed watery diarrhea, 5-10 episodes per day, with increasing frequency over the past 4 months. It was not associated with any blood in stool, fever or crampy abdominal pain. The patient had lost 12 kg of weight in the last few years. There was no history of tuberculosis, hypertension or diabetes mellitus.

On examination, the patient was oriented. There was mild pallor and bilateral cervical lymphadenopathy. Per abdominal examination was suggestive of mild hepatosplenomegaly. Local examination revealed symmetrical inflammatory arthritis of small joints of hands with positive 'hand grip' test.

Investigation revealed mild anemia (Hb: 10.5 gm %), leukocytosis (13,000/cu. mm) with predominant neutrophilia (10,000/cu. mm). Erythrocyte sedimentation rate (ESR) was raised (78 mm/hr); hypocalcemia was present (7.5 gm%). Anti-streptolysin-O (ASLO), rheumatoid factor (RF) and antinuclear antibody (ANA) were negative. C-reactive protein (CRP) was positive. Stool and urine culture showed no growth. Serum ferritin was significantly raised (13,000 ng/ml). Human immunodeficiency virus (HIV) serology, HBSAg, Monospot test for Ebstein Barr Virus (EBV) were nonreactive. ECHO and chest X ray were normal. Stool for routine microscopy and fecal fat content were noncontributory. IgA tissue transglutaminase and antiendomysial antibody were positive. Subsequently, the duodenal biopsy was suggestive of celiac disease (total villous atrophy with increase in intraepithelial lymphocytes) [Figure - 1]. Cervical lymph node biopsy was suggestive of reactive lymphadenitis. Ultrasonography of abdomen revealed mild hepatosplenomegaly. X-ray bilateral hands showed periarticular soft tissue swelling with reduced joint space in proximal interphalangeal joints, severe periarticular osteopenia and subluxation of metacarpophalangeal joints consistent with severe erosive inflammatory arthritis [Figure - 2].

The patient was started on gluten-free diet with low-dose steroid therapy. Her diarrhea improved significantly, although she found considerable relief in joint pain on methotrexate therapy only. When last seen, 8 months past the initiation of treatment, she was diarrhea free with acceptable joint symptoms on hydroxychloroquine (200 mg twice daily) only. (Steroids were tapered after 2 months, and methotrexate was stopped 6 months later).


 ¤ Discussion Top


Adult-onset Still's disease (AOSD) is a recently recognized systemic inflammatory disorder of unknown etiopathogenesis, which typically afflicts young adults. This diagnosis was popularized by a 1971 report by Sir Bywaters E. [4] Its clinical course is marked by systemic exacerbations and/or chronic arthritis, frequently with disease­-free intervals. The diagnosis of Still's disease is essentially that of exclusion. The diagnostic criteria for Still's disease are as in [Table - 1]. [s5]

A quotidian (daily, spiking) or 'double-quotidian' fever curve is a hallmark of the disease. The typical Still's rash is an evanescent, salmon pink macular or maculopapular rash, seen along with the spike of fever, predominantly affecting the trunk and proximal extremities. The rash can be induced by minor trauma (Koebner phenomenon). Some suggest that serum ferritin values above 3,000 ng/ml in a patient with typical symptoms, in the absence of infection, should lead one to consider the diagnosis of AOSD.

The usual joints affected are wrists, knees and ankles - in descending order. Approximately one-third of patients have chronic persistent disease with progressive joint damage.

Rare autoimmune manifestations like secondary sjogren syndrome, aseptic meningitis, cranial nerve palsies, interstitial nephritis and thrombotic thrombocytopenic purpura have also been described. [6]

The management of AOSD remains empirical, and there are few controlled studies describing the treatment till date. Most patients require steroids, and many need high doses for 6 months, followed by chronic maintenance therapy. There is some evidence that methotrexate is effective, and newer studies demonstrate efficacy with the tumor necrosis factor (TNF) alpha inhibitor, etanercept.

Considering the symptomatology of the patient, although systemic lupus erythematosus seemed plausible in light of the arthritis and constitutional symptoms, the negative ANA and lack of other diagnostic features made this diagnosis very unlikely.

The young age and absence of periodic acid-Schiff (PAS) positive macrophages in the duodenal biopsy sample ruled out the possibility of Whipple's disease.

Although joint symptoms may precede diarrhea in celiac disease, the articular involvement found in gluten-associated arthropathy is most frequently a non-erosive, nondeforming arthritis with axial or sacroiliac joint involvement - as against the erosive deforming arthritis in our patient. [7]

There are many features in our communication that make it unique but at the same time interesting. As it is, AOSD remains a painstakingly difficult clinical diagnosis, largely because of its rarity, protean manifestations and lack of pathognomic features or diagnostic tests. Further, recently Interleukin 18 (IL-18) has been named a key cytokine in the pathogenesis of AOSD. Serum IL-18 levels are increased in AOSD patients, and they are well correlated with serum ferritin levels and disease activity. [8] Interestingly, IL-18 levels have been found to be elevated in patients of celiac disease also. Moreover, the IL-18 levels correlate with IgA anti-transglutaminase antibody levels in these patients, suggesting a common immunopathogenesis. [9] We could not measure IL-18 in our patient as facilities for the same were not available at our setup. Nevertheless, our patient responded dramatically to gluten-free diet, thus establishing our treatment strategy. Whether there is an association of AOSD with celiac disease is worth pursuing and calls for the need to study further into the autoimmune pathophysiology of both these disorders.

 
 ¤ References Top

1.Wakai K, Ohta A, Tamakoshi A, Ohno Y, Kawamura T, Aoki R, et al. Estimated prevalence and incidence of adult still's disease: Findings by a nationwide epidemiological survey in Japan. J Epidemiol 1997;7:221-5.  Back to cited text no. 1  [PUBMED]  
2.Quemeneur T, Noel LH, Kyndt X, Droz D, Fleury D, Binaut R, et al. Thrombotic microangiopathy in adult Still's disease. Scand J Rheumatol 2005;34:399-403.  Back to cited text no. 2    
3.Miller ML. Clinical aspects of juvenile rheumatoid arthritis. Curr Opin Rheumatol 1997;9:423-7.   Back to cited text no. 3  [PUBMED]  
4.Bywaters EG. Still's disease in the adult. Ann Rheum Dis 1971;30:121-33.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol 1992;19:424-30.   Back to cited text no. 5  [PUBMED]  
6.Perez MG, Rodwig FR Jr. Chronic relapsing thrombotic thrombocytopenic purpura in adult onset still's disease. South Med J 2003;96:46-9.  Back to cited text no. 6    
7.Lubrano E, Ciacci C, Ames PR, Mazzacca G, Oriente P, Scarpa R. The arthritis of coeliac disease prevalence and pattern In 199 adult patients. Br J Rheumatol 1996;35:1314-8.  Back to cited text no. 7  [PUBMED]  
8.Arlet JB, Le Thi Huong DB, Pouchot J, Piette JC. Current concepts on the physiopathology of adult-onset Still's disease. Rev Med Interne 2005;26:549-56.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Merendino RA, Di Pasquale G, Sturniolo GC, Ruello A, Albanese V, Minciullo PL, et al. Relationship between IL-18 and sICAM-1 serum levels in patients affected by coeliac disease: Preliminary considerations. Immunol Lett 2003;85:257-60.  Back to cited text no. 9    


    Figures

  [Figure - 1], [Figure - 2]
 
 
    Tables

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