Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach.

BACKGROUND: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients. OBJECTIVE: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases. METHODS: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease. RESULTS: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL. CONCLUSION: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged.

Topical Medical Cannabis: A New Treatment for Wound Pain-Three Cases of Pyoderma Gangrenosum.

Pain associated with integumentary wounds is highly prevalent, yet it remains an area of significant unmet need within health care. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated. The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, noninvasive, self-administered, and display rapid onset of analgesia. Extracts derived from the cannabis plant have been applied to wounds for thousands of years. The discovery of the human endocannabinoid system and its dominant presence throughout the integumentary system provides a valid and logical scientific platform to consider the use of topical cannabinoids for wounds. We are reporting a prospective case series of three patients with pyoderma gangrenosum that were treated with topical medical cannabis compounded in nongenetically modified organic sunflower oil. Clinically significant analgesia that was associated with reduced opioid utilization was noted in all three cases. Topical medical cannabis has the potential to improve pain management in patients suffering from wounds of all classes.

Skin Signs of Rheumatoid Arthritis and its Therapy-Induced Cutaneous Side Effects.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that primarily affects the joints, but may exhibit extra-articular, including cutaneous, manifestations such as rheumatoid nodules, rheumatoid vasculitis, granulomatous skin disorders, and neutrophilic dermatoses. A large burden of cutaneous disease may be an indication of RA disease activity and the need for more aggressive treatment. Many of the therapeutic agents used to treat RA can also result in cutaneous adverse effects, which pose their own diagnostic and therapeutic challenges. Anti-TNFα agents, in particular, have a wide variety of adverse effects including psoraisiform eruptions, granulomatous conditions, and cutaneous connective tissue disorders. Herein we provide an update on the clinical presentations and management of RA-associated cutaneous findings as well as drug-induced cutaneous effects, with particular attention to the adverse effects of biologic disease-modifying agents.

Pyoderma gangrenosum: skin grafting and hyperbaric oxygen as adjuvants in the treatment of a deep and extensive ulcer.

Pyoderma gangrenosum is a rare dermatosis of unknown etiology and variable clinical presentation. The disease is challenging for the medical staff, from the frequent diagnostic difficulties to the lack of scientific evidence with a good level to support the management of extensive and refractory cases. Our patient is a 50 year-old man with an extensive and deep ulcer on the left leg, which exemplifies the therapeutic difficulties inherent to the disease and who, fortunately, has progressed with excellent result after association of hyperbaric oxygen therapy and skin grafting to the immunosuppression therapy initially proposed.

Pyoderma gangrenosum: skin grafting and hyperbaric oxygen as adjuvants in the treatment of a deep and extensive ulcer / Pioderma gangrenoso: enxerto de pele e oxigenoterapia hiperbarica como adjuvantes no tratamento de ulcera extensa e profunda

Pyoderma gangrenosum is a rare dermatosis of unknown etiology and variable clinical presentation. The disease is challenging for the medical staff, from the frequent diagnostic difficulties to the lack of scientific evidence with a good level to support the management of extensive and refractory cases. Our patient is a 50 year-old man with an extensive and deep ulcer on the left leg, which exemplifies the therapeutic difficulties inherent to the disease and who, fortunately, has progressed with excellent result after association of hyperbaric oxygen therapy and skin grafting to the immunosuppression therapy initially proposed.

Pioderma gangrenoso é dermatose rara de etiologia não completamente compreendida e apresentação clínica variável. A doença apresenta muitos desafios à equipe médica, desde a freqüente dificuldade diagnóstica até a inexistência de evidências científicas com bom nível para condução de casos extensos e refratários. Apresentamos o caso de um paciente masculino, 50 anos, com úlcera extensa e profunda em perna esquerda, que exemplifica bem a dificuldade terapêutica e que, felizmente, evoluiu com excelente resultado após associação de oxigenoterapia hiperbárica e enxertia de pele ao tratamento imunossupressor inicialmente proposto.

Pyoderma gangrenosum: guideline for wound practitioners.

Pyoderma gangrenosum (PG) is an atypical ulceration of the skin with unknown aetiology, usually associated with autoimmune systemic illnesses and haematological malignancies. Diagnosis is based on clinical suspicion and exclusion of other conditions. Treatment options vary greatly, ranging from conservative local and systemic immunosuppression to surgical measures, including amputation, but none is shown to be universally effective. Currently no guideline regarding escalation of treatment exists. Based on a review of the current literature and three illustrative cases of PG, a working treatment guideline is presented for wound practitioners.

Feasibility of conservative medical treatment for pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a chronic skin disease with an incidence of 3-10 per million, and it is often associated with underlying systemic disease. A case of PG of the left leg successfully treated with local debridement and advanced and compression dressings, without systemic treatment is reported. Progression and healing of the ulcer was incredibly rapid. The treatment of PG usually consists of systemic administration of corticosteroids. But wherever the administration of systemic immunosuppressive therapy is impractical, a topical treatment can be used. This type of treatment does not represent a mere palliative, but could be significant for healing, as in the case of our patient.

Oxigenoterapia hiperbárica como tratamento adjuvante do pioderma gangrenoso / Hyperbaric oxygen therapy as an adjuvant treatment for pyoderma gangrenosum

O pioderma gangrenoso é uma dermatose neutrofílica, rara da pele e do tecido subcutâneo, caracterizada por um processo necrosante progressivo e doloroso. A conduta no Pioderma gangrenoso requer, com frequência, o uso de drogas sistêmicas, tais como: corticoides, sulfonas e imunossupressoras, seja de maneira isolada, seja em combinação. Muitos relatos, na literatura, documentam o tratamento com êxito do Pioderma gangrenoso, com a oxigenoterapia hiperbárica. No nosso caso, uma jovem com lesões extensas e muito dolorosas, o tratamento com oxigenoterapia hiperbárica associado ao corticoide e imunossupressor promoveu cicatrização, com excelente resultado, com fechamento rápido da lesão e diminuição do desconforto.

Pyoderma Gangrenosum is a rare neutrophilic dermatosis of skin and subcutaneous tissue characterized by a painful and progressive necrotizing process. The management of pyoderma gangrenosum often requires systemic drug therapy, such as corticosteroids, sulfones or immunosuppressants, either alone or in combination. Several reports in the literature document the successful treatment of pyoderma gangrenosum with hyperbaric oxygen therapy. In our case, hyperbaric oxygen therapy associated with corticoids and immunosuppressants promoted healing of large and very painful lesions in an adolescent girl with an excellent outcome, including rapid wound closure and decreased discomfort.

The use of B vitamins for cutaneous ulcerations mimicking pyoderma gangrenosum in patients with MTHFR polymorphism.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) polymorphisms are associated with thrombophilia and vasculopathy that may result in cutaneous ulceration. Pyoderma gangrenosum (PG) is a clinical diagnosis that may be made following exclusion of alternate causes of ulceration, including vascular inflammatory or occlusive disease, infection, and malignant neoplasm. OBSERVATIONS: We describe 2 patients with MTHFR polymorphisms discovered during hypercoagulable evaluation for cutaneous ulcerations on the lower extremities. Both patients showed a rapid improvement following treatment with oral vitamin supplementation and local wound care. One patient developed several subsequent ulcers when he decided to discontinue his therapy, and following reinitiation of therapy, the new ulcerations healed. The treatment was tolerated well without any adverse effects. CONCLUSIONS: MTHFR polymorphisms should be part of a comprehensive laboratory evaluation during hypercoagulable workup. Vitamin supplementation with folic acid (B(9)), pyridoxine hydrochloride (B(6)), and cyanocobalamin (B(12)) may result in healing of cutaneous ulcerations in some patients with MTHFR mutations.

Hyperbaric oxygen therapy as an adjuvant treatment for pyoderma gangrenosum.

Pyoderma Gangrenosum is a rare neutrophilic dermatosis of skin and subcutaneous tissue characterized by a painful and progressive necrotizing process. The management of pyoderma gangrenosum often requires systemic drug therapy, such as corticosteroids, sulfones or immunosuppressants, either alone or in combination. Several reports in the literature document the successful treatment of pyoderma gangrenosum with hyperbaric oxygen therapy. In our case, hyperbaric oxygen therapy associated with corticoids and immunosuppressants promoted healing of large and very painful lesions in an adolescent girl with an excellent outcome, including rapid wound closure and decreased discomfort.

Subcorneal pustulosis and Pyoderma gangrenosum associated with a biclonal gammopathy.

Pyoderma gangrenosum and subcorneal pustulosis are two neutrophilic dermatoses. Their occurrence in the same patient is rare and may be related to an IgA dysglobulinemia. We report a case presenting these two conditions associated with a biclonal benign IgA and IgG gammopathy. A 67-year-old man exhibited typical pyoderma gangrenosum associated after three years duration with subcorneal pustulosis lesions, confirmed by cutaneous biopsy. Laboratory results showed a biclonal benign IgA and IgG kappa gammopathy. Therapeutic management was difficult: Pyoderma gangrenosum responded well to corticosteroids but subcorneal pustulosis management was harder and treatments were poorly effective.Pyoderma gangrenosum and subcorneal pustulosis are a part of the neutrophilic spectrum. Their association has been only reported in eleven patients. In eight cases, an IgA dysglobulinemia was associated suggesting its responsibility in the occurrence of both dermatoses. Treatments are various and not fully effective. If the Pyoderma gangrenosum usually responds to corticosteroids, the subcorneal pustulosis treatments are not well defined and often not efficient. Our case illustrates the dissociated evolution of these two dermatoses and their difficult global management. During the follow-up, a regular search for dysglobulinemia is required in order to detect malignant transformations.

Mycosis fungoides bullosa simulating pyoderma gangrenosum.

A patient with mycosis fungoides (MF) bullosa had a rapidly growing, painful necrotic mass on the left ankle which extended by peripheral bulla formation, clinically resembling pyoderma gangrenosum. Histopathology confirmed MF bullosa with both intraepidermal and subepidermal bulla formation.

Pyoderma gangrenosum of the orbit.

Pyoderma gangrenosum is an uncommon chronic ulcerative condition, the aetiology of which is poorly understood. Ophthalmic involvement is rare. The case presented in this paper involves destruction of the orbital contents with subsequent perforation of the eye despite conventional therapy. Evisceration was performed with the patient being subjected to hyperbaric oxygen therapy pre- and post-operatively, with resultant cessation of the disease process.