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Year : 2016  |  Volume : 59  |  Issue : 1  |  Page : 84-86
Adult-onset Still's disease with myocarditis and hemophagocytic lymphohistiocytosis: Rare manifestation with fatal outcome

1 Department of Pathology and Laboratory Science, Armed Forces Medical College, Command Hospital, Pune, Maharashtra, India
2 Department of Internal Medicine, Armed Forces Medical College, Command Hospital, Pune, Maharashtra, India

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Date of Web Publication9-Mar-2016


Adult-onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology characterized by fever, evanescent pink salmon rash, arthritis, and multiorgan involvement. Here, we report an unusual manifestation of AOSD in a 40-year-old male who presented to our hospital with pyrexia of unknown origin and rash of 3 weeks duration. All his serological investigations and imaging studies were unremarkable. He was fulfilling clinical and laboratory criteria as per Yamaguchi for AOSD and was managed for the same. Our patient did not respond well to the treatment, had a downhill course, and succumbed to his illness. Autopsy confirmed myocarditis and florid bone marrow reactive hemophagocytosis as the cause of his death.

Keywords: Adult-onset Still′s disease, hemophagocytic lymphohistiocytosis, myocarditis

How to cite this article:
Gupta D, Jagani R, Mendonca S, Rathi KR. Adult-onset Still's disease with myocarditis and hemophagocytic lymphohistiocytosis: Rare manifestation with fatal outcome. Indian J Pathol Microbiol 2016;59:84-6

How to cite this URL:
Gupta D, Jagani R, Mendonca S, Rathi KR. Adult-onset Still's disease with myocarditis and hemophagocytic lymphohistiocytosis: Rare manifestation with fatal outcome. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Jan 24];59:84-6. Available from: https://www.ijpmonline.org/text.asp?2016/59/1/84/174825

   Introduction Top

Adult-onset Still's disease (AOSD) is a disease, which was first described by George Still in 1897 in children, but it was not until 1971 that AOSD was recognized as a clinical entity by Bywaters. [1] The disease has varied clinical expression and unpredictable progression. [2] It is a disease of exclusion once the infectious, neoplastic, and autoimmune causes are ruled out. Patients present with high spiking fevers, arthralgias or arthritis, sore throat, transient maculopapular rash, lymphadenopathy, hepatosplenomegaly, and serositis. Patients may or may not have all of the above symptoms at onset. AOSD has a favorable prognosis if identified and treated early, however, often because of delay in diagnosis it leads to life-threatening events. Acute interstitial myocarditis and reactive hemophagocytic syndrome in the bone marrow has rarely been reported as a complication of AOSD. [3],[4] Here, we report the case of a 40-year-old male with AOSD who died from complications of interstitial myocarditis and reactive hemophagocytic syndrome, which was confirmed at postmortem.

   Case report Top

A 40-year-old male with no comorbidities was admitted to our hospital with complaints of fever of 20 days duration. Fever was intermittent, moderate to high grade, and associated with chills. He also gave a history of sore throat, decreased appetite, and multiple joint pains involving symmetrical small joints of hands, wrists, ankles, knees, and lower back. The fever was also associated with maculopapular rash involving the trunk, back, and both upper extremities. There was no history of vomiting, loose motions, and photosensitivity. On admission, the vital parameters were as follows: Body temperature - 99.8F, pulse rate - 88/min, and blood pressure - 110/70 mmHg. There was no lymphadenopathy, pedal edema or icterus. Physical examination revealed tenderness in elbows, wrists, knees and ankle joints, and skin rash over the trunk and both upper extremities [Figure 1].
Figure 1: Typical maculopapular stills rash distributed on chest and forearm (antemortem)

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Systemic examination revealed mild hepatomegaly. Laboratory investigations done at admission indicated white blood count was 16,800/mm 3 with 88% neutrophils (polymorphonuclear leukocytosis). Platelets were more than 450,000/mm 3 (reactive thrombocytosis). His erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated to 40 mm/h (normal range 1-20 mm/h) and 24 mg/L (normal range <06 mg/L), respectively. The serum ferritin level was increased to 16,500 ng/ml (normal range - 15-150 ng/ml). Serological tests done included venereal disease research laboratory, Widal, HIV, Anti-HBsAg, Anti-HCV, Dengue, Brucella, Epstein-Barr virus Leptospira, which were all negative. His antinuclear antibody (ANA), dsDNA, and rheumatoid factor (RF) were negative. Repeated blood cultures, urine and stool cultures showed no growth. His serum lactate dehydrogenase was raised to 740 U/L (normal range 200-400 IU/L). Liver function tests were mildly deranged with aspartate transaminase being 86 IU/L and alanine transaminase at 125 IU/L. Bone marrow aspirate and biopsy were reported as cellular reactive marrow. Patient was empirically started on broad spectrum injectable antibiotics, antimalarials, and antipyretics. Meanwhile patient underwent contrast enhanced computed tomography of the chest, abdomen, and pelvis, which revealed bilateral pre- and para-tracheal and mesenteric lymphadenopathy. Two-dimensional echocardiography done showed mild pericardial effusion only. Because of such heterogeneous clinical and laboratory findings fitting into Yamaguchi's criteria [1] a differential of AOSD was considered. Steroids 1 mg/kg/day were added in the treatment regime. However, our patient developed azotemia, hypotension with metabolic acidosis. He was placed on a mechanical ventilator and started on inotropes. In spite of aggressive management patient succumbed to his illness 10 days after his admission to our hospital. An autopsy was performed on the deceased. At autopsy, the heart was enlarged and weighed 450 g with mild pericardial effusion. The pericardial surface was smooth, glistening, and there were no pericardial adhesions. The heart was opened by inflow and outflow tract method and the myocardium, valve leaflets, coronaries were grossly unremarkable. On histology, the myocardium showed edema and extensive mononuclear inflammatory infiltrate comprising chiefly of lymphocytes with few plasma cells and histiocytes [Figure 2]. There was no histological evidence of pericarditis. The histology of the bone marrow biopsy showed diffuse proliferation of macrophages with evidence of hemophagocytosis amidst the normal hematopoietic elements [Figure 3]a and b]. No significant changes were observed in lungs, spleen, and liver. The kidneys showed features of acute tubular necrosis. Histological examination of pre- and para-tracheal, mesenteric lymph nodes showed reactive hyperplasia.
Figure 2: Postmortem (H and E, ×100) section from the myocardium shows diffuse interstitial infiltration by mononuclear inflammatory cells

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Figure 3: (a) Postmortem (H and E, ×100) section of bone marrow biopsy shows florid hemophagocytosis (indicated by arrow). The activated histiocytes show marked phagocytosis of all hematopoietic elements. (b) immunohistochemical stain for CD68 highlights the macrophages

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   Discussion Top

AOSD is a rare multisystem inflammatory disorder of unknown etiology that generally affects young adults. The etiology remains unknown, however, infective agents especially viruses are thought to trigger the illness in genetically susceptible individuals. [5] AOSD is characterized by high spiking fever, evanescent maculopapular rash, arthralgias or arthritis, hepatosplenomegaly, lymphadenopathy, and sore throat. Patients often have polymorphonuclear leukocytosis while other markers of any connective tissue disorders such as ANA, RF are negative. ESR, CRP, and serum ferritin levels were increased. High levels of serum ferritin are characteristic of AOSD, [6] and it indicates disease activity due to macrophage activation. Patients of AOSD usually have varied disease manifestations, which can involve any organ system. Patients may have pulmonary manifestation ranging from pleuritis to pneumonitis, renal manifestations presenting as proteinuria and nephrotic syndrome, neurological symptoms as well as cardiac abnormalities such as pericarditis, pericardial tamponade, and myocarditis. [7] Myocarditis has been rarely described with AOSD. Only a few cases of interstitial myocarditis are reported in the literature. [8],[9] In our case, the diagnosis of myocarditis was established at postmortem. Hemophagocytic syndrome is also a rare complication of AOSD.

It has been reported in 12% cases of AOSD. It is known as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome. HLH is also characterized by fever, hepatosplenomegaly, increased ferritin levels all of which are also features of AOSD. In HLH, however, there are cytopenias and decreased ESR, which is contrary to increased ESR and leukocytosis seen in AOSD flares. Bone marrow trephine biopsy helps to confirm hemophagocytosis, however, it is important to note that the absence of hemophagocytosis can occur in 20% of initial bone marrow specimens as was noted in our case. [10]

Treatment includes nonsteroidal anti-inflammatory drugs, corticosteroids, immunosuppressants that is, methotrexate, azathioprine, etc. Biological agents that are, anti-interleukin-6 (IL-6), anti-TNF alpha, anti-IL-7 are being used in refractory cases.

AOSD has protean manifestations and can be associated with life-threatening complications such as hemophagocytic syndrome, liver failure, and myocarditis.

Our case is unusual as the patient had myocardial involvement along with HLH. Because of multiple organ systems involvement our patient did not respond to treatment and succumbed to his disease.

   Conclusions Top

AOSD is a complex systemic disorder and poses both diagnostic and therapeutic challenges to the clinicians. Diagnosis is based on the exclusion of other infective, neoplastic, and connective tissue diseases.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Bywaters EG. Still's disease in the adult. Ann Rheum Dis 1971;30:121-33.  Back to cited text no. 1
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. 2
Dhote R, Simon J, Papo T, Detournay B, Sailler L, Andre MH, et al. Reactive hemophagocytic syndrome in adult systemic disease : Report of twenty-six cases and literature review. Arthritis Rheum 2003;49:633-9.  Back to cited text no. 3
Colina M, Govoni M, Trotta F. Fatal myocarditis in adult-onset Still's disease with diffuse intravascular coagulation. Rheumatol Int 2009;29:1355-7.  Back to cited text no. 4
Escudero FJ, Len O, Falcó V, de Sevilla TF, Sellas A. Rubella infection in adult onset Still's disease. Ann Rheum Dis 2000;59:493.  Back to cited text no. 5
Meijvis SC, Endeman H, Geers AB, ter Borg EJ. Extremely high serum ferritin levels as diagnostic tool in adult-onset Still's disease. Neth J Med 2007;65:212-4.  Back to cited text no. 6
Reginato AJ, Schumacher HR Jr, Baker DG, O'Connor CR, Ferreiros J. Adult onset Still's disease : e0 xperience in 23 patients and literature review with emphasis on organ failure. Semin Arthritis Rheum 1987;17:39-57.  Back to cited text no. 7
Vandergheynst F, Gosset J, van de Borne P, Decaux G. Myopericarditis revealing adult-onset Still's disease. Acta Clin Belg 2005;60:205-8.  Back to cited text no. 8
Kristensen LE, Bartosik I. Myocarditis in adult-onset Still's disease despite significant immunosuppressive therapy. Scand J Rheumatol 2006;35:330-1.  Back to cited text no. 9
Aricò M, Janka G, Fischer A, Henter JI, Blanche S, Elinder G, et al. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996;10:197-203.  Back to cited text no. 10

Correspondence Address:
Devika Gupta
Department of Pathology and Laboratory Science, Armed Forces Medical College and Command Hospital, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.174825

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  [Figure 1], [Figure 2], [Figure 3]

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