Dramatic Response of Familial Majeed Syndrome to Interleukin-1 Antagonist Therapy: Case report.

Majeed syndrome (MS) is a rare, autosomal recessive, autoinflammatory disease characterized by recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and inflammatory dermatome. In this article, we report the cases of two siblings with MS. Genetic studies of both siblings were obtained and revealed mutations in LPIN2 gene by means of a homozygous single-base pair change in the donor splice site of exon 17 (c.2327+1G>C). Both patients underwent different modalities of treatment for MS which involved immune-suppressive and biologic therapies. We observed a significant clinical response to biologic anti-interleukin-1 (IL-1) therapy in our patients. This impressive clinical response indicates the pivotal role of IL-1 in MS pathogenesis. There are limited data on the use of anti-IL-1 therapy in treating MS due to the rarity of the condition. Anti-IL-1 therapy should be considered as a promising treatment for this disease.

Renal manifestations in hypocomplementic urticarial vasculitis syndrome: Is it a distinct pathology?

Hypocomplementic urticarial vasculitis syndrome (HUVS) is an autoimmune disease characterized by recurrent urticaria, arthritis, and glomerulonephritis (GN). Anti-C1q antibody is the marker of HUVS together with low levels of classical pathway complements which are C2, C3, C4, and C1q. We report a case of a 6-year-old boy who presented with episodes of rashes, injected conjunctiva, abdominal pain, and arthritis, diagnosed as HUVS. He had low C3, low CH50, normal C4, and positive C1q antibody. His urinalysis showed intermittent microscopic hematuria only. One year later, his laboratories showed persistent low C3 and positive Anti-ds DNA. The urinalysis showed hematuria, pyuria, and nephrotic-range proteinuria. Urine protein to creatinine ratio was 101.8 h mg/mmol. Kidney biopsy showed mesangioproliferative GN consistent with the diagnosis of HUVS. The patient was treated initially with prednisolone then azathioprine was added to the regimen. He showed good response with the disappearance of hematuria and proteinuria. Nine months later, he had no skin rashes with normal urinalysis and normal anti-ds DNA antibody. We report a case with HUVS and GN with positive anti-dsDNA antibody that revealed good response to combination of immunosuppressive therapy.

Hypocomplementemic Urticarial Vasculitis Syndrome in an 8-year-old Boy: A Case Report and Review of Literature.

Hypocomplementemic urticarial vasculitis syndrome is an immune complex-mediated disease of unknown etiology. The clinical course is characterized by urticaria, conjunctivitis, joint pain, and hypocomplementemia. We here report a case of a child with hypocomplementemic urticarial vasculitis syndrome that progressed to nephritis. Renal biopsy was consistent with diffuse proliferative glomerulonephritis with diffuse subendothelial immune deposits. He responded well to a combination of steroid and mofetil micofenolate.

Pediatric-onset Behçet disease in Bahrain: report of nine cases and literature review.

BACKGROUND: This report studies the clinical features of Behçet disease (BD) in children and compares our results with other international studies. METHODS: We retrospectively reviewed patient data that included the clinical picture, HLA typing, and treatment in BD cases. RESULTS: This study reviewed data from a total of nine children with BD. Median age at presentation was seven years, with a male to female ratio of 2:1. There was one patient who had Down's syndrome. Oral ulcers were present in all children, while genital ulcers were present in only 66% of cases. Skin manifestation was seen in 88% and uveitis in 55%. There was evidence of gastrointestinal (55%), neurological (55%), and musculoskeletal manifestations (77%). HLA B5 was positive in 66% of cases and 55% had positive family histories. Apart from gastrointestinal symptoms, our results were comparable with other studies. CONCLUSION: Awareness of BD symptoms in the pediatric age group is crucial for early diagnosis and treatment. The coexistence of BD and Down's syndrome needs further genetic study, which may link these two major disorders.

Juvenile systemic lupus erythematosus in Bahrain. A tertiary referral center experience.

OBJECTIVE: To analyze the clinical and serological features of children with systemic lupus erythematosus (SLE) in a major referral center in Bahrain and to assess the comorbidity, its morbidity, and mortality. METHODS: We retrospectively reviewed the medical charts of children with SLE treated in the Pediatric Rheumatology Clinic at Salmaniya Medical Complex, Kingdom of Bahrain from 1998 to 2007. The ethical approval for the study was obtained from the Research Health Committee, Ministry of Health, Kingdom of Bahrain. RESULTS: Thirty-two children with SLE were identified. Thirty-one (96.8%) were Bahrainis. The mean age was 14 +/- 4 years, the mean age of disease onset was 9 +/- 4 years and the mean duration of illness was 7 +/- 5 years. The female to male ratio was 2.5:1. Twenty-five percent of the cases had relatives with SLE. Eight patients (25%) had sickle cell anemia (SCA). Systems involved were as follows: skin (93%), kidney (81%), musculoskeletal system (65%), blood (56%), gastrointestinal tract (31%), central nervous system (31%), lungs and cardiovascular system (21%). Serological tests showed: positive antinuclear antibody in 90.6%, and positive anti double-stranded DNA antibody in 65%. The morbidity rate was 21% (n=7) due to complication and 12.5% (n=4) died. CONCLUSION: Clinical and serological results were comparable with the international studies. Nephritis was the primary cause of morbidity and mortality. Coexistence of SLE with SCA was also reported in other studies and may need further investigation with genetic studies.

A splice site mutation confirms the role of LPIN2 in Majeed syndrome.

Majeed syndrome is an autoinflammatory disorder consisting of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and neutrophilic dermatosis. To date, 2 unrelated families with Majeed syndrome have been reported. Mutations in LPIN2 have been found in both families. Here we report a third consanguineous family with Majeed syndrome with a novel mutation. The patient, a 3-year-old Arabic girl, had hepatosplenomegaly and anemia as a neonate. At age 15 months, she developed recurrent episodes of fever and multifocal osteomyelitis. In addition, bone marrow aspiration demonstrated significant dyserythropoiesis, suggesting Majeed syndrome. Coding sequences and splice sites of LPIN2 were sequenced in the patient and her mother. A homozygous single-basepair change was detected in the donor splice site of exon 17 (c.2327+1G>C) in the patient; her mother was heterozygous at this site. These data confirm the role of LPIN2 mutations in the etiology of Majeed syndrome.