Tumor-necrosis-factor Receptor Associated Periodic fever Syndrome (TRAPS) is characterized by periodic fever, cutaneous rash, conjunctivitis, lymphadenopathy, abdominal pain, myalgia and arthralgia [1]. Several cases of TRAPS are caused by about 80 identified mutations in the gene encoding the tumour necrosis factor receptor super family1A (TNFRSF1A) on chromosome 12p13. A subset of patients with a clinical profile suggestive of TRAPS with no mutations in the TNFRSF1A gene has been described, thus suggesting that not all mutations are yet known or that alternative mechanisms might be involved in the pathogenesis [2].

A 11-year-old boy presented in June 2006 with a 2 year history of recurrent fevers with irregular periodicity, intermittent periumbilical abdominal pain and urticarial rash. Table I describes the chronology of events.

TABLE I  Timeline of Events in our Patient 

In February 2011, the clinical history was reviewed when the child presented again with fever. Considering the prolonged and suggestive clinical profile, a diagnosis of TRAPS was entertained, and mutation testing for TRAPS for the child and parents was requested. Mutations in exons 2,3,4, and 5 of TNFRSF1A gene tested negative. A clinical diagnosis of mutation negative TRAPS (TRAPS like illness) was made, and the child was started on etanercept at a dose of 0.4 mg/kg biweekly in November 2011. His response was dramatic with no fever episodes or illness for next since 1.5 years. He had a weight gain of 6 kg and a height gain of 10 cms. Owing to cost considerations, the etanercept dose has been titrated to reduce its frequency. He currently needs etanercept once every 23-24 days to remain symptom free. Two efforts of increasing the interval further led to breakthrough fever, fatigue and rash.

More than 200 cases of TRAPS have been described in international medical literature, with majority of the reports from South and Central Europe. TRAPS is the most common autosomal dominant auto-inflammatory disorder, homogenously distributed among different ethnic groups [3]. An extensive review of literature did not reveal any case reports on TRAPS from India. Age of onset has been reported to range from the first year of life to 53 years. The characteristic features include recurrent fevers of varying duration, abdominal pain, and recurrent cutaneous and synovial inflammation. Migratory myalgia, with overlying migratory erythematous rash, due to monocytic fasciitis, is a specific feature that distinguishes it from the other periodic fever syndromes. Abdominal pain due to serositis is seen in 92% patients, which may sometimes lead to unnecessary abdominal surgery [4]. Ocular symptoms include periorbital edema, conjunctivitis, uveitis and iritis. TRAPS in pediatric age group is most easily confused with systemic onset juvenile idiopathic arthritis, due to fever and migratory rash or inflammatory bowel disease due to the triad of fever, anemia and raised ESR.

Laboratory investigations during episodes typically show an acute phase response, neutrophilia, and thrombocytosis. In addition anemia of chronic disease may be seen. Some, patients have low levels of the soluble tumour necrosis factor (TNF) receptor levels, both during and in between episodes [4]. We were unable to perform this test.

The TNFRFS1A gene, located on short arm of chromosome 12, encodes a 55 kDa receptor for TNF, called TNFR1 [2]. Literature suggests that overall a genetic diagnosis can be made only in less than 35% patients fitting the clinical phenotype of an auto inflammatory syndrome [4]. Aganna, et al. reported no mutation in 8 out of 18 families, and in 172 out of 176 sporadic cases consistent with clinical diagnosis of TRAPS [5].

Treatment options in TRAPS include non-steroidal anti-inflammatory drugs, and intermittent corticosteroids, as the first line [6]. The identification of the mutation in TNFRSF1A gene led to the use of anti–TNF drugs, in particular etanercept for the treatment. Etanercept also acts as a steroid sparer and reduces the number of disease flares, symptoms and severity of an attack. A 6 month clinical trial with etanercept at a dose of 0.5 mg per kg twice weekly reported global clinical and biological improvement [7, 8]. Pediatric cases have also been treated efficiently with etanercept [7]. In our patient, we used a modified and individualized regimen of etarnercept after clinical titration, thus achieving disease free periods of about 23 days and reducing the cost of therapy significantly.

Acknowledgments: Dr Ivona Aksentijevich, Clinical Genetics Services, Inflammatory Disease Section, National Human Genome Research Institute, National Institute of Health for performing the genetic testing for TRAPS for our patient.

Contributors: AD: wrote the manuscript and reviewed the literature; RPK: worked up and followed the case.

Funding: None; Competing interests: None stated.

1. Chen YJ, Yu HH, Yang YH, Lau YL, Lee WI, Chiang BL. Recurrent abdominal pain as the presentation of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in an Asian girl: A case report and review of the literature. J Microbiol Immunol Infect. 2012; Aug 23. [E-.pub ahead of print].

2. Cantarini L, Lucherini OM, Cimaz R, Rigante D, Baldari CT, Laghi Pasini F, et al. Typical and severe tumor necrosis factor receptor-associated periodic syndrome in the absence of mutations in the TNFRSF1A gene: a case series. Rheumatol Int. 2012;32:4015-8.

3. Baron L, Athreya B, Kastner D. Periodic fever syndromes and other autoinflammatory disorders. In: Cassidy JT, Petty RE, Laxer RM, Lindsley CB, editors. Textbook of Pediatric Rheumatology. 6th ed. Philadelphia: Saunders Elsevier 2011. P. 647.

4. Bodar EJ, Dreanth JPH, van der Meer JWM, Simon A. Dysregulation of innate immunity, hereditary periodic fever syndromes. BrJ Hematol. 2009;144:279–302.

5. Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, et al. Heterogeneity among patients with tumor necrosis factor receptor–associated periodic syndrome phenotypes. Arthritis Rheum. 2003;48:2632-44.

6. Jacobelli S, André M, Alexandra JF, Dodé C, Papo T. Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS) Rheumatology. 2007;46:1211-2.

7. Drewe E, McDermott EM, Powell PT, Isaacs JD, Powell RJ. Prospective study of anti-tumour necrosis factor receptor superfamily 1B fusion protein, and case study of anti-tumour necrosis factor receptor superfamily 1A fusion protein, in tumour necrosis factor receptor associated periodic syndrome (TRAPS): clinical and laboratory findings in a series of seven patients. Rheumatol. 2003;42:235–9.