Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases.

Treatment and outcome of systemic lupus erythematosus (SLE) in C1q deficient patients are rarely reported. The aim of this report is to share our experience about the course of management of three cases diagnosed as SLE with C1q deficiency, in light of present literature. Initial and dominant complaints of three cases from two different families were cutaneous manifestations. One patient was also diagnosed with arthritis and thrombocytopenia. Antinuclear antibody was positive in all cases, whereas anti-dsDNA was negative with normal levels of complement C3, C4 and decreased CH50 activity. C1QA gene of two patients had homozygous nonsense mutation (c.622 > T/p.Gln208Ter). Previously, all of them had been treated with steroids, hydroxychloroquine and methotrexate or azathioprine. It was learned that they had responded only to high dosage prednisolone and their symptoms flared up during dosage reduction even under methotrexate or azathioprine. All symptoms of all three cases improved by daily fresh frozen plasma (FFP) infusions, and once cutaneous lesions subsided, the infusions were reduced to a frequency that would prevent the flare up of the symptoms. Literature search revealed seven reports on fresh frozen plasma treatment in SLE with C1q deficient patients. In this report, it is concluded that severe cutaneous lesions, as seen in these C1q deficient SLE patients, cannot be controlled with conventional immunosuppressive treatment. Instead, regular fresh frozen plasma infusions are proposed as a more reasonable method of treatment.