Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency.

Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.

Acne Fulminans: Case Series and Review of the Literature.

Acne fulminans (AF) is a rare manifestation and the most severe form of the entire clinical spectrum of acne. The disease is destructive and is characterized by the sudden onset of painful and ulcerative pustules and systemic symptoms including high fever, hepatomegaly, polyarthralgia, leukocytosis, plaquetose, and increased inflammatory markers and transaminases. Osteolytic lesions in multiple skeletal sites could also be associated. The use of isotretinoin is considered a related trigger, as well as the use and cessation of testosterone, although a bacterial infection, a drug-induced disease, or an intake of anabolic androgenic steroids has been suggested. The treatment of AF is challenging and controversial. The recommended treatment is aggressive and consists of a combination of oral steroids and low doses of isotretinoin, with no consensus at this time. The patient may require several weeks of hospitalization to control the eruption. The cutaneous lesions usually leave scars and milia. We report on two boys and two girls presenting with AF, triggered by isotretinoin in three patients and by an antibiotic in one patient. All the patients treated with corticosteroids and isotretinoin with success.

Severe Skin Complications After Small Bowel Transplantation: Graft-Versus-Host Disease, DRESS, Virus, or Drug Toxicity?

BACKGROUND: Severe skin problems are uncommon after small bowel transplantation. Differential diagnosis includes drug reactions, infections, graft-versus-host disease (GVHD), and mixed diseases. Early diagnosis and treatment are determinant for prognosis. METHODS AND RESULTS: We describe 6 patients with severe cutaneous complications after small bowel transplantation, the work-up, final diagnosis, and evolution. Two patients died from chronic GVHD or unrecognized drug rash with eosinophilia and systemic symptoms, the others recovered completely. In 2 patients, drugs and viruses could be implicated, and in 1 patient may have hidden or triggered chronic GVHD. Viruses (human herpesvirus 6, Epstein-Barr virus, and cytomegalovirus) were suspected to trigger drug rash with eosinophilia and systemic symptoms or GVHD. The 2 cases of acute GVHD were reversed completely by increased immunosuppression and anti-interleukin-2 receptor antibody. DISCUSSION: In these severe cases, diagnosis is urgent and should include a careful evaluation of drug history, clinical presentation, biological investigations, infections, and toxic screening. A skin biopsy and chimerism study should be performed whenever possible. An early treatment is key to a positive outcome.