Adult-onset still's disease, an unusual cause of severe acute liver injury: A case report.

Adult-onset Still's disease is a systemic inflammatory disease that often presents with spiking fever, typical rash, arthritis, and serositis. However, adult-onset-Still's-disease associated liver injury and acute liver failure are rare. Herein, we report a case of acute liver injury in a 23-year-old female patient with adult-onset Still's disease. She presented to the emergency department with a high fever and sore throat. She was then admitted to the department of infectious diseases with a preliminary diagnosis of an atypical respiratory infection. After being treated with antibiotics and antiviral agents, she was discharged. A few days later, she returned to the emergency department with jaundice and was rehospitalized. This time, she was admitted to the department of gastroenterology, where she was diagnosed with adult-onset Still's disease-associated acute liver injury. Eventually, the patient responded to immunosuppressive treatment with significant clinical improvement.

Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations.

OBJECTIVE: To prospectively monitor inflammatory activity over a prolonged period in a cohort of Turkish patients with FMF, their healthy relatives and healthy controls and to relate this to their MEFV genotypes. METHODS: 43 patients with FMF and 75 of their asymptomatic relatives underwent fortnightly assessments and venesection for measurement of CRP and SAA over 5 months. 50 unrelated healthy population matched controls were also studied. MEFV genotyping was performed on all participants and comparisons were made between the different groups. RESULTS: Paired MEFV mutations were detected in 84% of FMF patients and single mutations in 12%. Substantial acute phase reactivity was seen among the patients with FMF during attacks (median SAA 693 mg/l, CRP 115 mg/l). Between attacks there was also some inflammatory activity (median SAA 6 mg/l, CRP 4 mg/l). Among healthy controls 16% were heterozygotes for MEFV mutations and 4% had two mutations. As expected there was a substantial carrier rate among healthy relatives with mutations detected in almost 92%. Asymptomatic MEFV heterozygotes had elevated acute phase proteins compared to wild type subjects. CONCLUSION: Substantial sub-clinical inflammation occurs widely and over prolonged periods in patients with FMF, indicating that the relatively infrequent clinically overt attacks represent the 'tip of the iceberg' in this disorder. Both basal and peak acute phase protein concentrations were greater in MEFV heterozygotes than in wild-type controls, regardless of mutation demonstrating a 'pro-inflammatory' phenotype among FMF carriers. Upregulation of the acute phase response among carriers of FMF may augment their innate host response and contribute to better resistance to infection.

The effect of interferon alpha administration on acute attacks of familial Mediterranean fever: A double-blind, placebo-controlled trial.

BACKGROUND: About a quarter of familial Mediterranean fever (FMF) patients are partially or totally resistant to colchicine. A previous observation reported that acute attacks may be shortened by administration of interferon alpha (IFN). OBJECTIVE: We designed a double-blind, placebo-controlled trial to test our initial observations of a beneficial response with IFN in FMF attacks. METHODS: We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the early phase of the attack. Leucocytes, thrombocytes, the erythrocyte sedimentation rate, fibrinogen, C-reactive protein (CRP), serum amyloid A protein (SAA), haptoglobin, transferrin, IL-1beta and TNF-alpha were measured at hours 0, 6, 12, 24 and 48. RESULTS: The median time to recovery in those treated with IFN and placebo was not significantly different, while the leucocytosis and high levels of fibrinogen were significantly more prolonged in placebo-treated patients. CRP and SAA were extremely elevated and peaked at 24h, remaining less marked in the IFN-treated patients but the difference was not statistically significant. Observations regarding the other parameters were unremarkable. CONCLUSIONS: Although there were some clues indicating a depressed inflammatory response with IFN, we could not demonstrate a definitive effect of this agent in this double-blind trial. The drug may suppress the acute inflammation of FMF only if administered at the earliest phase. CRP and SAA may be more sensitive indicators of an attack than ESR or fibrinogen.

The genetic basis of autosomal dominant familial Mediterranean fever.

Familial Mediterranean fever (FMF) is classically an autosomal recessive periodic inflammatory disease occurring in Mediterranean and Middle Eastern populations. It is caused by mutations affecting both alleles of MEFV, a gene that encodes pyrin (marenostrin), an uncharacterized neutrophil protein. Occasional reports of autosomal dominant FMF have often been discounted, on the basis that asymptomatic FMF carriers are common in certain populations, and give rise to pseudo-dominant inheritance. We performed comprehensive MEFV genotyping in five families in whom FMF appeared to be inherited dominantly. Transmission proved to be pseudo-dominant in two cases, but true dominant inheritance of FMF with variable penetrance was supported by the genotyping results in the other three families. The disease in these cases was associated with heterozygosity for either pyrin DeltaM694 alone or the compound pyrin variant E148Q/M694I, the latter occurring in two unrelated families. Complete MEFV sequencing failed to identify any coding region abnormality in the other allele in any of these cases, and, in the largest kindred, single-allele disease transmission was further supported by analysis of silent single nucleotide polymorphisms, which proved that affected individuals had at least three different complementary alleles. Studies of two further unrelated British patients with FMF associated with simple heterozygosity for pyrin DeltaM694 were also consistent with autosomal dominant inheritance. The clinical features of dominantly inherited FMF were absolutely typical, including AA amyloidosis in a patient with pyrin DeltaM694. These findings extend the spectrum of FMF, and suggest that the methionine residue at position 694 makes a crucial contribution to pyrin's function, and that a 50% complement of normal pyrin activity does not prevent susceptibility to FMF.

Coexistence of familial Mediterranean fever with sacroiliitis and Behçet's disease: a rare occurrence.

Familial Mediterranean fever (FMF) and Behçet's disease are relatively rare but may still coexist in the same patient. Sacroiliitis is another feature whose significance is controversial in either of the diseases. We report a case of longstanding FMF with sacroiliitis who later developed typical characteristics of Behçet's disease. Although occurrence by chance cannot be ruled out, this unusual patient may enhance the claims that FMF and Behçet's disease have common aetiopathogenetic mechanisms. It would be appropriate to include this coexistence in the list of differential diagnoses of the two diseases.

Long-term results of cryotherapy on malignant epithelial tumors of the conjunctiva.

We studied the results of combined treatment with excision and cryotherapy with the nitrous oxide probe in 22 eyes of 20 patients with intraepithelial tumors or squamous cell carcinomas of the conjunctiva. Patients were followed up for five to 12 years. Only two recurrences (9%) were seen, both of which occurred within the first two years. Over the long term, excision combined with cryotherapy decreased the recurrence rate of intraepithelial tumors and squamous cell carcinomas of the conjunctiva.