Familial Mediterranean fever (FMF) is a febrile disease characterized by acute, spontaneously resolving episodes of fever and pain caused by serosal inflammation and associated with mutations in the FMF gene, MEFV. Prophylaxis is maintained with colchicine. To our knowledge, no study has yet shown an association between FMF and cirrhosis of the liver. We conducted the current study to describe cryptogenic cirrhosis in FMF and to examine the possible relationship between the 2 entities. Patients with chronic liver disease were retrospectively identified through a computer search of a registry of 6000 patients with FMF followed in the clinics of the National Center for FMF. Data pertaining to FMF phenotype and genotype and characteristics of the liver disease were abstracted from patients' charts. Cryptogenic cause of cirrhosis was determined by exclusion of known causes of liver disease. Nine patients with cryptogenic cirrhosis were identified, comprising 0.15% of the FMF patient population, a rate significantly higher than the rate of 0.015% of cirrhosis of all types expected in the total population of Israel (p < 0.000). Most patients had typical FMF, with a normal severity score distribution. The mean daily dose of colchicine was 1.4 +/- 0.4 mg, not different from the usual dose. All 7 patients who underwent mutation analysis had 2 mutations. Five of them were homozygous for M694V. Child-Pugh classification was determined in 6 patients at the time of cirrhosis diagnosis, and was classified as A in 4 of them. These findings suggest that MEFV may serve as a modifier gene in cryptogenic cirrhosis. Genetic analysis in patients with cryptogenic cirrhosis unrelated to FMF, particularly patients of a Mediterranean origin, may be warranted in future studies.

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Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted. Methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, and IVIg may be beneficial in improving the skin tightness in SSc. Calcium channel blockers, the angiotensin II receptor type 1 antagonist losartan, prazocin, the prostacyclin analogue iloprost, N-acetylcysteine and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. Epoprostenol and bosentan are approved for therapy of pulmonary hypertension (PAH). Other options under investigation include intravenous or aerolized iloprost. Cyclophosphamide (CYC) pulse therapy is effective in suppressing active alveolitis. Stem cell and lung transplantation is a viable option for carefully selected patients. Renal crisis can be effectively managed when hypertension is aggressively controlled with angiotensin converting enzyme (ACE) inhibitors. Patients should continue taking ACE inhibitors even after beginning dialysis in hope of discontinuing dialysis. Anti-thymocyte globulin and mycophenolate mofetil appear safe in SSc. The improvement in skin score and the apparent stability of systemic disease during the treatment period suggest that controlled studies of these agents are justified. Stem cell transplantation is under investigation for severe disease. Novel therapies are currently being tested in the treatment of SSc and have the potential of modifying the disease process and overall clinical outcome. The evaluation of these studies is still a difficult process.