Alessandro Borghi

Cutaneous manifestations in patients with inflammatory bowel diseases: Pathophysiology, clinical features, and therapy

Abstract:The skin is one of the most common extraintestinal organ system affected in patients with inflammatory bowel disease (IBD), including both Crohns disease and ulcerative colitis. The skin manifestations associated with IBD are polymorphic and can be classified into 4 categories according to their pathophysiology: (1) specific, (2) reactive, (3) associated, and (4) induced by IBD treatment. Cutaneous manifestations are regarded as specific if they share with IBD the same granulomatous histopathological pattern: perianal or metastatic Crohns disease (commonly presenting with abscesses, fistulas or hidradenitis suppurativa-like features) is the prototype of this setting. Reactive cutaneous manifestations are different from IBD in the histopathology but have close physiopathological links: pyoderma gangrenosum, a neutrophil-mediated autoinflammatory skin disease typically manifesting as painful ulcers, is the paradigm of this group. Among the cutaneous diseases associated with IBD, the most commonly seen are erythema nodosum, a form of panniculitis most commonly involving bilateral pretibial areas, and psoriasis, a T helper 1/T helper 17–mediated erythematous squamous inflammatory disease. Finally, the number of cutaneous adverse reactions because of IBD therapies is progressively increasing. The most frequent drug-induced cutaneous manifestations are psoriasis-like, eczema-like, and lichenoid eruptions, as well as cutaneous lupus erythematosus for biologics, and nonmelanoma skin cancer, mainly basal cell and squamous cell carcinomas for thiopurines.

Pyoderma gangrenosum and its syndromic forms: Evidence for a link with autoinflammation

Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro‐IL)‐1β to its active isoform IL‐1β. The overproduction of IL‐1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil‐mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well‐known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.

Oral clindamycin and rifampicin in the treatment of hidradenitis suppurativa‐acne inversa: a prospective study on 23 patients

Editor Hidradenitis Suppurativa-Acne Inversa (HS-AI) is a relapsing and chronic inflammatory skin disease affecting the big folds. HS-AI is currently thought of as being an inflammatory and not an infectious disease, but sometimes various bacteria combined in polymicrobial infections can be present. Coagulasenegative staphylococcus and anaerobic bacteria are the most frequently isolated. The bacteria are suspected of playing a role in the disease process, probably through immune-mediated mechanisms of inflammation. Therapy of HS-AI is often difficult. Medical, surgical and physical therapeutical options are available. Although antibiotics are widely used to treat HS-AI limited data on their efficacy are available. To assess the efficacy and the tolerability of a 10-week combination of oral clindamycin (600 mg daily) and rifampicin (600 mg daily) in the treatment of HS-AI, 23 patients affected by severe and actively inflammatory HS-AI were enrolled in a prospective non comparative study. The ethical committee considered as not needed its official consensus to precede. No restrictions about previous treatments were established. The parameters used to evaluate the efficacy of the treatment were as follows: (i) severity of the disease, assessed with the Sartorius score before (T0) and after (T1) treatment and (ii) the number of exacerbations during the treatment period compared with those occurring in the previous three months. The authors considered as exacerbation the acute development of at least one wide inflammatory lesion. Finally, patients were asked about side-effects during treatment. Statistical analysis was performed using parametric test (t-test). Significance was accepted at P < 0.05. The main clinical-demographic data, collected in a standardized form, are summarized in Table 1. Three patients did not complete the treatment: one for personal reasons, one because of gastro-intestinal side-effects not related to Clostridium difficile colitis, and one, affected by amyotrophic lateral sclerosis, complained of a worsening of the neurological disease, probably not related to antibiotic assumption. The 20 patients who completed the 10-week therapy showed a mean Sartorius score of 132.05 (range 28.00–298.05) at T0 and 71.50 (range 19.50–183.00) at T1 corresponding to a mean reduction of 45.85% (range 5.41–81.95%). The authors considered as responders the 17 patients who achieved a Sartorius score improvement higher than 25%, corresponding to the 85% of the patients who completed the treatment. The mean number of exacerbations was 6.00 (range 1.00–20.00) at T0 and 2.40 (range 0–10.00) at T1 corresponding to a mean reduction of 60% (range 0–100%). Both Sartorius score and the number of exacerbations showed a significant reduction after treatment: P = 0.00098 for Sartorius score and P = 0.0091 for the number of exacerbations, respectively. Three out of 23 patients (13.04%) complained of side-effects, mostly nausea and vomiting: one patient stopped the therapy before the scheduled end, whereas the two remaining completed the 10-week treatment. The efficacy and tolerability of this combination treatment in HS-AI has previously been assessed in three retrospective studies. The present one is the first prospective study and the results are in agreement with those reported in literature (Table 2). The reason why this antibiotic combination is effective is not fully understood yet. This study has some limitations. The patients were not randomized vs. placebo or other treatments. This decision was made for ethical reasons and because, in the authors’ experience, this treatment is the best option in severe HS-AI in terms of efficacy, tolerability, quick onset of action and cost. No data about long-term follow-up and recurrences are given because a maintenance treatment with oral zinc was prescribed, according to the desire of the patients to do as much as possible to maintain the results they had obtained.

Proactive maintenance therapy with a topical corticosteroid for vulvar lichen sclerosus: preliminary results of a randomized study.

The chronic and relapsing nature of vulvar lichen sclerosus (VLS) represents a challenge for its long‐term management after an effective treatment with topical corticosteroids.

Use of topical herbal remedies and cosmetics: a questionnaire-based investigation in dermatology out-patients.

Background Although topical remedies and cosmetics based on herbal ingredients are becoming increasingly popular with the public due to the perception that botanical compounds are safer and healthier than their synthetic counterparts, a large number of adverse cutaneous effects of plant extracts, notably contact sensitization, have been reported in medical literature.

First randomized trial on clobetasol propionate and mometasone furoate in the treatment of vulvar lichen sclerosus: results of efficacy and tolerability

A 3‐month topical application of clobetasol propionate (CP) represents the recommended and accepted first‐line treatment for vulvar lichen sclerosus (VLS); however, to date, no randomized controlled trials have compared the efficacy and safety of CP with other topical corticosteroids.

Prospective Clinical and Epidemiologic Study of Vulvar Lichen Sclerosus: Analysis of Prevalence and Severity of Clinical Features, together with Historical and Demographic Associations

Background: Few reports have addressed the associations between clinical, demographic and historical variables of vulvar lichen sclerosus (VLS). Objective: To elaborate the prevalence and severity of signs and symptoms and to identify potential factors predicting the severity and course of VLS. Methods: A prospective cohort of 225 patients affected by VLS was included. Data were collected by direct interview and clinical examination. Results: 98% of patients complained of symptoms, principally itching. Pallor and scarring-sclerosis-atrophy were the most frequent and severe signs. The severity of VLS signs was not associated with age at onset and duration of the disease. About 70% of the patients had previously undergone treatment. Conclusions: VLS-related symptoms were not associated with the clinical features which resulted less severe. Personal history of autoimmune diseases and familial history of VLS did not influence the age at onset and the severity of VLS. A considerable part of patients had previously received inappropriate treatment.

Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in achieving stable remission

Background  Aimed at the reduction of post‐treatment relapse of severe acne, the cumulative dose of oral isotretinoin should be ≥120 mg/kg. However, data on the appropriate oral isotretinoin treatment regimen in mild and moderate acne are lacking.

Topical botanically derived products: use, skin reactions, and usefulness of patch tests. A multicentre Italian study

The evidence on the safety of topical preparations containing botanical extracts is limited.

Sweet's Syndrome: A Retrospective Clinical, Histopathological and Immunohistochemical Analysis of 11 Cases

The aim of this paper is to report our clinical experience of Sweets syndrome, a severe dermatological disease which may be extremely important to recognize for the early diagnosis of a neoplastic disorder. Eleven patients affected by Sweets syndrome, treated at the Department of Dermatology, University of Ferrara, Ferrara, Italy, during 1998 to 2004, were evaluated. A retrospective analysis was performed. Data on age, sex distribution, clinical data, histopathological and immunohistochemical findings and therapy were collected. We observed one patient with idiopathic form, 5 patients affected by the para-inflammatory variant and 5 para-neoplastic cases (with haemoproliferative diseases). The cases with the para-inflammatory form were affected by minor infectious manifestations. Prolonged follow-up is necessary to verify that a case of idiopathic variant is not really a paraneoplastic form. Based on immunohistochemical analysis, we cannot exclude that true histiocytes, immunoreactive for CD68/PGM, infiltrate the dermis in Sweets syndrome lesions.