Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

[Exanthem, erythrodermia]

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Gluten intolerance and skin diseases.

International audienceGluten sensitivity with or without coeliac disease (CD) symptoms and intestinal pathology has been suggested as a potentially treatable cause of various diseases. CD is a chronic disease which improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. There have been numerous reports linking CD with several skin conditions. A body of evidence shows that dermatitis herpetiformis is actually a cutaneous manifestation of CD. Autoimmune diseases, allergic diseases, psoriasis and miscellaneous diseases have also been described with gluten intolerance. Dermatologists should be familiar with the appraisal of gluten sensitive enteropathy and should be able to search for an underlying gluten intolerance (GI). Serological screening by means of antigliadin, antiendomysial and transglutaminase antibodies should be performed. HLA typing is often useful in association with serologic tests. Intestinal biopsy is usually needed to establish the diagnosis of CD or GI. Thus, gluten intolerance gives rise to a variety of dermatological manifestations which may benefit from a gluten-free diet

[Facial dermatosis: acne, rosacea, seborrhoeic dermatitis]

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[Locoregional polymorphous Pseudomonas aeruginosa skin infection.]

International audienceA 72-year-old diabetic woman was referred with a painful chronic leg ulcer associated with venous and arterial insufficiency. She then developed a polymorphous skin infection due to Pseudomonas aeruginosa, with ecthyma gangrenosum, subcutaneous abscess and panniculitis of the homolateral inferior limb, without general sepsis. Although P. aeruginosa infection may induce polymorphous skin lesions, they are most often observed in immunocompromised patients following septicaemia

Genital human Papillomavirus infection in patients with autoimmune inflammatory diseases.

International audienceTreatment advances achieved over the last few years have radically changed the management of patients with autoimmune inflammatory diseases requiring conventional or biological immunosuppressive therapy. These diseases and the drugs used to treat them increase the rate of infections, including genital infections due to the human Papillomavirus (HPV). Genital HPV infections have been extensively studied in organ transplant recipients, HIV-infected patients, and patients with congenital immune deficiencies. Although genital HPV infections usually manifest as benign lesions of the external genital organs (condylomata), they are associated with an increased risk of cancer. Very few data are available on genital HPV infections associated with autoimmune inflammatory diseases or their treatments. Here, we review the published information on this topic