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Year : 2022  |  Volume : 20  |  Issue : 2  |  Page : 104-106

A patient with recurrent fever – TRAPped for diagnosis!

1 Departments of General Medicine, Yashoda Hospital, Hyderabad, Telangana, India
2 Departments of Rheumatology, Yashoda Hospital, Hyderabad, Telangana, India
3 Departments of Cardiology, Yashoda Hospital, Hyderabad, Telangana, India

Date of Submission20-Jan-2022
Date of Decision27-Feb-2022
Date of Acceptance01-Mar-2022
Date of Web Publication07-May-2022

Correspondence Address:
Dr. Hari Kishan Boorugu
Department of General Medicine, Yashoda Hospital, Somajiguda, Hyderabad - 500 082, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cmi.cmi_8_22

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Hereditary recurrent fever syndromes are rarely diagnosed in India, and the age at diagnosis is usually childhood or early adulthood. We present an adult male patient with recurrent fever since childhood who presented to us at 59 years of age and was subsequently diagnosed to have TNFR1-associated periodic fever syndrome that responded well to colchicine.

Keywords: Adult, fever, hereditary, recurrent, TNFR1-associated periodic fever syndrome

How to cite this article:
Boorugu HK, Irlapati RV, Jariwala PV, Jadhav KP. A patient with recurrent fever – TRAPped for diagnosis!. Curr Med Issues 2022;20:104-6

How to cite this URL:
Boorugu HK, Irlapati RV, Jariwala PV, Jadhav KP. A patient with recurrent fever – TRAPped for diagnosis!. Curr Med Issues [serial online] 2022 [cited 2022 Aug 15];20:104-6. Available from: https://www.cmijournal.org/text.asp?2022/20/2/104/344937

  Introduction Top

Pyrexia of unknown origin is still a challenging scenario for physicians despite progress of diagnostic medicine. Periodic fever syndromes are rare in India, and many physicians do not come across patients with periodic fever syndromes and often do not consider this diagnostic possibility in differential diagnoses, especially among older adults. We hereby describe a patient who was symptomatic since childhood but diagnosed to have TNFR1-associated periodic fever syndrome (TRAPS) in the 6th decade of life.

  Case Report Top

A 59-year-old man presented with recurrent fever for 1 year. He had four episodes of fever, each episode lasting 3–4 weeks. The fever was associated with rash at times, and he had no localizing symptoms or signs on history and clinical examination. The rash was urticarial in nature, and it usually involved the abdominal wall and trunk. He had been evaluated in detail elsewhere. He had received antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) with some relief. He came to us for further evaluation. His baseline investigations were normal except for leukocytosis and elevated C-reactive protein (CRP), which was documented during previous episodes of fever as well. His malarial smears, human immunodeficiency virus serology, antinuclear antibody, Brucella antibody, and antineutrophil cytoplasmic antibody (ANCA) tests were negative. Computerized tomogram of the chest, bone marrow evaluation, transesophageal echocardiogram, and whole-body positron emission tomography and computed tomography were noncontributory. He was diagnosed to have probable ANCA-negative vasculitis in view of leukocytosis in the absence of infection, elevated inflammatory markers, and recurrent fever associated with rash. He was started on oral prednisone (0.5 g/kg body weight) and his fever resolved within a week's time. He returned to us with recurrence of fever while on a tapering dose of steroids. On re-evaluating his history, he was found to have recurrent episodes of fever since childhood, but the frequency was once or twice a year. He had increased frequency and longer duration fever episodes for a year, sometimes triggered by stress. His elder brother also has recurrent fever episodes. In view of this history, the possibility of periodic fever was considered and TRAPS mutation analysis was performed. A pathogenic variant of TNF-alpha receptor gene (TNFRSF1A, location exon 2, variant c. 175T >c, heterozygosity) was detected, and he was diagnosed to have TRAPS. Two months after he was diagnosed to have TRAPS, his granddaughter was admitted elsewhere with recurrent fever and she was also detected to have pathogenic variant of gene mutation for TRAPS suggesting the presence of a hereditary disease in the family. The patient was evaluated for secondary amyloidosis. His abdominal fat pad biopsy was negative for amyloid on Congo red staining. Serum amyloid A protein, an acute-phase reactant in inflammatory disorders, was elevated. His steroid dose was tapered and stopped, and he was started on colchicine. He had no recurrence of fever in the last 5 months, his white blood cell count and CRP were normal, and he had no proteinuria at 5-month review.

The authors have obtained signed informed consent from the patient. In the form, the patient has given his consent for his clinical information to be reported in the journal.

  Discussion Top

Auto-inflammatory conditions are disorders of innate immunity without an identifiable antigen and autoantibodies.[1] There are several of such syndromes, familial Mediterranean fever syndrome being the most common among them. TRAPS is another similar auto-inflammatory disease characterized by recurrent fever lasting 3–4 weeks, rash, periorbital swelling, and sometimes pleurisy.[2] The onset of symptoms is usually in the first decade of life.[2] The Eurofever/ the Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria may be used to diagnose hereditary recurrent fevers [Table 1].[3]
Table 1: The Eurofever/PRINTO classification criteria for TNFR1-associated periodic fever syndrome

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If a patient meets these criteria, has episodes of recurrent inflammation, elevated acute-phase reactants and undergoes evaluation to rule out other confounding diseases, we can make a diagnosis of periodic fever syndrome with high accuracy. Our patient meets the criteria for the diagnosis of TRAPS.[3] A significant proportion of patients with TRAPS develop amyloidosis, with approximately 10%–15% of patients developing clinical manifestations of secondary amyloidosis.[4],[5] Our patient had no evidence of amyloidosis on abdominal fat pad biopsy, but his serum amyloid A protein level was elevated. Serum amyloid A protein is an acute-phase reactant in rheumatic diseases, but its role in predicting amyloidosis is not clear. Treatment of a typical attack includes NSAIDs or steroids.[6] Treatment options for patients with recurrent, severe attacks include antitumor necrosis factor therapy (etanercept), anti-interleukin-1 therapy (canakinumab), and occasionally interleukin-6 receptor antagonist tocilizumab.[7],[8] Colchicine has been used in some patients with complete or partial response, but we do not know the impact of colchicine on potential amyloidosis risk.[9] Our patient responded well to colchicine. He had no recurrence of fever till his last review 5 months after initiation of therapy. TRAPS is a rare disease and is likely to be missed, especially in older adults with fever of unknown origin. Although very rare, we need to consider the possibility of hereditary recurrent fever syndromes in older patients with recurrent fever and elevated acute-phase reactants.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

De Sanctis S, Nozzi M, Del Torto M, Scardapane A, Gaspari S, de Michele G, et al. Autoinflammatory syndromes: Diagnosis and management. Ital J Pediatr 2010;36:57.  Back to cited text no. 1
Toro JR, Aksentijevich I, Hull K, Dean J, Kastner DL. Tumor necrosis factor receptor-associated periodic syndrome: A novel syndrome with cutaneous manifestations. Arch Dermatol 2000;136:1487-94.  Back to cited text no. 2
Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis 2019;78:1025-32.  Back to cited text no. 3
Lachmann HJ, Papa R, Gerhold K, Obici L, Touitou I, Cantarini L, et al. The phenotype of TNF Receptor-Associated Autoinflammatory Syndrome (TRAPS) at presentation: A series of 158 cases from the Eurofever/EUROTRAPS international registry. Ann Rheum Dis 2014;73:2160-7.  Back to cited text no. 4
Cantarini L, Rigante D, Merlini G, Vitale A, Caso F, Lucherini OM, et al. The expanding spectrum of low-penetrance TNFRSF1A gene variants in adults presenting with recurrent inflammatory attacks: Clinical manifestations and long-term follow-up. Semin Arthritis Rheum 2014;43:818-23.  Back to cited text no. 5
ter Haar NM, Oswald M, Jeyaratnam J, Anton J, Barron KS, Brogan PA, et al. Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis 2015;74:1636-44.  Back to cited text no. 6
Cantarini L, Lucherini OM, Muscari I, Frediani B, Galeazzi M, Brizi MG, et al. Tumour necrosis factor receptor-associated periodic syndrome (TRAPS): State of the art and future perspectives. Autoimmun Rev 2012;12:38-43.  Back to cited text no. 7
La Torre F, Muratore M, Vitale A, Moramarco F, Quarta L, Cantarini L. Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Rheumatol Int 2015;35:1943-7.  Back to cited text no. 8
Vitale A, Sota J, Obici L, Ricco N, Maggio MC, Cattalini M, et al. Role of colchicine treatment in tumor necrosis factor receptor associated periodic syndrome (TRAPS): Real-life data from the AIDA network. Mediators Inflamm 2020;2020:1936960.  Back to cited text no. 9


  [Table 1]


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