Diffuse Skin Tightness in Familial Mediterranean Fever: A Case Report and Review of Literature

Elham Behrangi1, Nasrin Shayanfar2, Hadi Mohagheghian Yaghoubi3, Saman Aghabekloo4, Zahra Azizian5

1 Department of Dermatology, Rasoul-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

2 Department of Pathology, Rasoul-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

3 Department of Immunology, Shahid Sadughi University of Medical Science, Yazd, Iran

4 Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

5 Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran

Introduction

Familial Mediterranean Fever (FMF) is an autosomal recessive inherited and inflammatory disorder characterized by periodic episode of fever, peritonitis, pleurisy and arthritis. The most common symptoms consist of abdominal pain, typical chest pain and myalgia [1, 2]. If left untreated, amyloidosis causes renal failure frequently. Cutaneous involvement of FMF occurs in 7% to 10% of patients. Erysipelas-like erythema is the most common and known skin lesion of FMF; however, other clinical involvements of skin such as vasculitis and paniculitis may be seen in patients with FMF. Some diseases are associated with FMF, which include Behcet’s disease [3], IBD and lupus erythematosus [4], but there has not been shown any association between systemic sclerosis and FMF in studies. Hence, we report a case of FMF with Diffuse skin tightness.

Case Presentation

An 18-year-old girl known as a case of FMF for 3 years presents to our department with tight skin since childhood. She does not have any family history of FMF. Its disease diagnose was confirmed by genetic analysis. There was hemozygotic mutation in MEFV on chromosome 16. The stiffness of skin was progressive. It first appeared when she was about 7 years old. She had a history of autoimmune hepatitis at age of 6, cochlea implantation at age 8 and also she went under surgery due to accessory left side breast. During past 3 years, she had taken Colchicine irregularly and three flares of disease had occurred but there were no cutaneous lesions coincided with flare of disease or the interval between flares. In physical examination, tight skin with general induration in all surfaces of skin, sclerodactyly (Figure1) and beaked nose microstomia (Figure2) are noticed.

The clinical features of systemic sclerosis such as Raynaud’s phenomenon, digital ulcers and internal organ manifestations all are absent. Special auto antibodies which are positive in systemic sclerosis such as ANA, anti-dsDNA, anti-centromere and anti-scl70 are negative. All differential diagnosis of scleroderma includes skin changes such as gammopathy (by immune electrophoresis), mucin deposition (by biopsy), drug and chemical induced disorders (by history taking) are ruled out. There was no evidence of lung fibrosis in spiral computed tomography (CT) scan and also manometry and barium enema of esophagus was normal. All biochemical and hematological laboratory tests are normal. Histopathology of skin did not show special finding, just little acanthosis and hyperkeratosis. In addition, increased level of elastin and collagen in dermis was present (Figure3). For medical ethics consideration, all figures are presented with eye blinding and with permission of patient.

Discussion

FMF is AR inherited disease caused by mutation in MEFV located on chromosome 16p [5, 6]. One clinical skin lesion of it is erysipelas which is quite common in FMF, although others such as paniculitis and recurrent bullous dermatosis [7] are occasionally described in FMF.

Some mutations in Mediterranean fever gene appear to result in the disease in a vast majority of cases. This gene produces a protein called pyrin or marenostrin. The protein is expressed mostly in neutrophils and may act as an inhibitor of chemotactic factor (C5a) or perhaps of interleukin8 (IL8). Individuals with normal pyrin/marenostrin levels would have the ability to deactivate the chemotactic factors when it is produced in response to an inflammatory process. However, patients with FMF lack such ability resulting in uninhibited activity of the chemotactic factor and episodes of inflammation in the peritoneum, pleura, skin and joints. These also may lead to inflammatory episodes and excess production of amyloids that all would result in skin tightness [8].

In a case report by Bafounta et al. [9] two unusual skin lesions of FMF which are diffuse; sweet’s syndrome like reactions and lichenified erysipelas like are reported. Our report is particular because of atypical scleroderma like skin presentation in a patient with FMF disease. There are some similarities in pathogens of FMF and systemic sclerosis. The cytokines of immune system (IL4 and TNFα) [10-13] which have great roles in collagen synthesis and inducing inflammation are present in both mentioned diseases. This report can lead some authors to hypothesize the effect of mentioned cytokines on scleroderma like skin presentation in FMF disease.

Conclusion

Finally, FMF should be considered as a differential diagnosis in patients attending with skin tightness and the possible etiology is cytokines.