Summary Background Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. Objectives To investigate the association of variants of the MEFV gene with a complex HS phenotype. Methods Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. Results The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4·2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16·50–99·84, P < 0·001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2·80 (95% CI 1·31–5·97, P < 0·001). Conclusions The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

No abstract

Sterol-C4-methyl oxidase (SC4MOL) deficiency was recently described as an autosomal recessive cholesterol biosynthesis disorder caused by mutations in the <i>MSMO1</i> (sometimes also referred to as <i>SC4MOL</i>) gene. To date, 5 patients from 4 unrelated families with SC4MOL deficiency have been reported. Diagnosis can be challenging as the biochemical accumulation of methylsterols can affect global development and cause skin and ocular pathology. Herein, we describe 2 siblings from a consanguineous Turkish family with SC4MOL deficiency presenting with psoriasiform dermatitis, ocular abnormalities (nystagmus, optic hypoplasia, myopia, and strabismus), severe intellectual disability, and growth and motor delay. We undertook whole-exome sequencing and identified a new homozygous missense mutation c.81A&#x3e;C; p.Asn27Thr in <i>MSMO1</i>. Segregation analysis in all available family members confirmed recessive inheritance of the mutation. The siblings were treated with a combination of oral and topical statin and cholesterol which resulted in clinical improvement. This study demonstrates how genomics-based diagnosis and therapy can be helpful in clinical practice.

BackgroundEpidermolysis bullosa pruriginosa (EBP) is rare a clinical variant of dystrophic epidermolysis bullosa characterized by trauma‐induced bullae formation, milia and nail dystrophy accompanied by severe pruritus. Treatment pruritus of EBP focuses on immunosuppressive treatment with limited efficacy. Treatment strategies are not well‐established.AimTo provide the genetic characterization of a multi‐generational EBP family and discuss the efficacy of intravenous immunoglobulin treatment in EBP.Materials & methodsThe clinical characteristics of patients diagnosed with EBP in three consecutive generations were determined. The mutation is analyzed in the index patient's genomic DNA by Sanger sequencing, and this mutation was confirmed in other affected members of the family. Index case with severe phenotype was treated with intravenous immunoglobulin (IVIG).ResultsA heterozygous single nucleotide transition, c.6127G>A, in exon 73 of COL7A1 was identified in all affected members. Physical examination of patients revealed lichenoid papules on extensor surfaces of extremities, excoriations, milia formation and nail dystrophy. Majority of patients had elevated serum IgE levels (%86 (6/7)) without a medical history for atopy. Female patients had generalized involvement and severe phenotype. The skin lesions of the index case were refractory to high dose systemic steroids and cyclosporine treatment. Lesions improved significantly with intravenous immunoglobulin therapy.ConclusionIn severe cases, unresponsive to other therapies, IVIG may be a preferable therapeutic approach to modulate the inflammatory response in patients with EBP.

No abstract