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PubMed2001

[Acne inversa: a dapsone-sensitive dermatosis].

Acne inversa is a chronic disease with a major impact on the quality of life. Therapeutic options were long restricted to local disinfectants and systemic antibiotics, as well as repeated incision and drainage which produce only short term benefits. Retinoids, antiandrogens and radiation therapy are only partially successful. The best approach appears to be surgical removal of the entire apocrine sweat gland apparatus. Dapsone is used in dermatology to treat inflammatory dermatoses such as dermatitis herpetiformis and pyoderma gangrenosum, and was formerly the treatment of choice for acne conglobata. We report its successful use in acne inversa. Five female patients aged 23-40 years with acne inversa for a mean of 9.6 years were included. All patients showed an almost complete resolution of their symptoms within 2-4 weeks. All patients rated the treatment results with dapsone as good or very good. The treatment was well tolerated and no important side effects occurred. Because of its lack of teratogenicity, dapsone may be the most favorable treatment option in young women with acne inversa.

Acne Vulgaris↗
PubMed1998

Lack of correlation of skin thickness with bone density in patients receiving chronic glucocorticoid.

The objective was to test the hypothesis that there is a correlation between thinning of the skin and bone in patients on chronic oral glucocorticoids (GCs). This was a one-time cross-sectional analysis performed in an academic referral center. The study group consisted of 14 patients on GCs for a variety of disorders, including dermatomyositis, pemphigus vulgaris, pyoderma gangrenosum, and urticarial vasculitis. Skin thickness was compared with that of 24 sex- and age-matched controls. The main outcome measures were the bone density of the lumbar spine (L2-L4) and the skin thickness. The skin thickness (mm, mean +/- SEM) in GC-treated (n = 7) vs unmedicated age-matched Caucasian women (n = 20) was 0.84 +/- 0.04 vs 1.02 +/- 0.04 (t = 3.07, P < 0.01) in the upper arm, 1.13 +/- 0.09 vs 1.49 +/- 0.05 (t = 3.65, P < 0.002) in the dorsal forearm, and 0.96 +/- 0.07 vs 1.17 +/- 0.02 (t = 2.92, P < 0.01) in the ventral forearm. L2-L4 bone densities averaged 106 +/- 2% in the GC-treated female patients relative to the age and sex-matched controls. There was no correlation between skin thickness and bone density. In GC-treated (n = 4) vs unmedicated Caucasian men matched for age (n = 4), skin thickness was 1.09 +/- 0.4 vs 1.33 +/- 0.05 (t = 3.51, P < 0.02) in the upper arm, but was not significantly different at the two forearm sites. No correlation between skin thickness and bone density was observed. The level of type I procollagen mRNA in skin from three GC-treated patients was 45% of the value in three age-matched controls. In conclusion, GCs cause statistically significant thinning of skin independently of the effects on bone.

Absorptiometry, Photon↗
PubMed2000

Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in childhood: a report of ten cases and review of the literature.

UNLABELLED: Chronic recurrent multifocal osteomyelitis is a rare chronic inflammatory musculoskeletal process observed in children and young adults. Recently, the acronym SAPHO syndrome (for synovitis, acne, pustulosis, hyperostosis, osteitis) was coined to emphasise the association between osteo-articular inflammations and different skin abnormalities which are aseptic and filled with neutrophils. In adults, chronic recurrent multifocal osteomyelitis is now a classical manifestation of SAPHO syndrome. Chronic skin disorders were seen in eight of ten children on follow-up at the University Children's Hospitals in Bern and Zurich and in 61 of 260 paediatric cases reported in the literature. The different skin lesions were palmoplantar pustulosis (n = 40), non-palmoplantar pustulosis (n = 6), psoriasis vulgaris (n = 16) or severe acne (n = 4). More rarely Sweet syndrome (n = 2) or pyoderma gangrenosum (n = 1) were reported. CONCLUSION: The synovitis, acne, pustulosis, hyperostosis, osteitis syndrome is pertinent even in paediatrics since skin involvement is frequent.

Acquired Hyperostosis Syndrome↗
PubMed2006

Restorative proctocolectomy for pediatric patients with ulcerative colitis.

PURPOSE: A restorative proctocolectomy has become an elective surgical treatment for patients with ulcerative colitis (UC). In children with UC, however, the role of this procedure has not yet been well evaluated. We investigated the postoperative status of pediatric patients with UC regarding the side effects of steroids, postoperative complications, and growth. METHODS: The medical records of 15 patients with UC who underwent a restorative proctocolectomy between August 1993 and October 2003 were retrospectively reviewed. RESULTS: Their mean age was 12.6 +/- 3.4 years (range 5.7-15.7; boys: 9, girls: 6). All patients had total colitis, except for one who had left-sided colitis. The mean cumulative dose of preoperative prednisolone was 6201 +/- 7980 mg (mean +/- SD). The operative indications were an unsuccessful response to medical treatments in 12 patients (80%) and severe colitis in 3 patients (20%). Surgery was performed in one stage in 6 patients and in two stages in 9 patients. Seven patients (47%) demonstrated growth retardation at the time of operation. Steroid-related complications were seen in 3 cases, i.e., steroid myopathy, glaucoma, and cataracts, respectively. As early postoperative complications, an intestinal obstruction was seen in 2 patients, peritonitis in 1, and pancreatitis in 1. As late complications, anastomotic stenosis was observed in 5 patients, pouchitis in 4, residual proctitis in 3, and anal or proctovaginal fistula in 2. An intestinal obstruction, peristomal pyoderma gangrenosum, and dehydration each was seen in 1 patient. A growth "catch-up" was obtained for all but one patient. All patients became free of corticosteroids. CONCLUSION: A restorative proctocolectomy was found to be an effective treatment alternative even in children with UC when conservative therapy proves to be ineffective.

Adrenal Cortex Hormones↗
PubMed2004

A review of the use of infliximab to manage cutaneous dermatoses.

BACKGROUND: Infliximab is a chimeric monoclonal antibody that binds specifically to human tumor necrosis factor-alpha (TNF-alpha), decreasing the effect of the cytokine in inflammatory diseases. OBJECTIVE: The aim of this study was to review the efficacy and safety of infliximab in the treatment of dermatological diseases. METHODS: A MEDLINE search (1966-January 2003), using the keyword "infliximab" was performed to find relevant articles pertaining to the use of infliximab in dermatology. RESULTS: Infliximab has been used in the following dermatological diseases: psoriasis, Behcet's disease, graft versus host disease, hidradenitis suppurativa, panniculitis, pyoderma gangrenosum, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome, sarcoidosis, subcorneal pustular dermatosis, Sweet's syndrome, toxic epidermal necrolysis, and Wegener's granulomatosis. There is a generally good safety profile for infliximab, which is similar to that when it is used to treat Crohn's disease and rheumatoid arthritis. CONCLUSION: Although not approved for use in dermatological diseases, there have been numerous reports of the efficacy of infliximab in cutaneous inflammatory diseases. The most promise lies in those diseases that have increased amounts of TNF-alpha in the cutaneous lesions, such as psoriasis.

Antibodies, Monoclonal↗
PubMedDate not supplied

Cutaneous effects of smoking.

BACKGROUND: Cigarette smoking is the single biggest preventable cause of death and disability in developed countries and is a significant public health concern. While known to be strongly associated with a number of cardiovascular and pulmonary diseases and cancers, smoking also leads to a variety of cutaneous manifestations. OBJECTIVE: This article reviews the effects of cigarette smoking on the skin and its appendages. METHODS: A literature review was based on a MEDLINE search (1966-2004) for English-language articles using the MeSH terms cutaneous, dermatology, tobacco, skin, and smoking. An additional search was subsequently undertaken for articles related to smoking and associated mucocutanous diseases, with the focus on pathogenesis and epidemiologic data. Articles presenting the highest level of evidence and latest reports were preferentially selected. RESULTS: Smoking is strongly associated with numerous dermatologic conditions including poor wound healing, wrinkling and premature skin aging, squamous cell carcinoma, psoriasis, hidradenitis suppurativa, hair loss, oral cancers, and other oral conditions. In addition, it has an impact on the skin lesions observed in diabetes, lupus, and AIDS. The evidence linking smoking and melanoma, eczema, and acne is inconclusive. Anecdotal data exist on the possible protective effects of smoking in oral/genital aphthosis of Behçet's disease, herpes labialis, pyoderma gangrenosum, acral melanoma, and Kaposi's sarcoma in AIDS patients. CONCLUSIONS: An appreciation of the adverse cutaneous consequences of smoking is important. Dermatologists can play an integral role in promoting smoking cessation by providing expert opinion and educating the public on the deleterious effects of smoking on the skin.

Humans↗
PubMed2005

Off-label dermatologic uses of anti-TNF-a therapies.

BACKGROUND: Tumor necrosis factor-alpha (TNF-a) is a proinflammatory cytokine that plays an immunomodulatory role in a variety of systemic and dermatologic diseases. Currently, three anti-TNF-a drugs are available in North America- infliximab (approved in the U.S. for the treatment of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, ulcerative colitis, and psoriatic arthritis), etanercept (approved in the U.S. for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis), and adalimumab (approved for the treatment of rheumatoid arthritis and psoriatic arthritis). OBJECTIVE: To review the current literature supporting alternative (and currently off-label) dermatologic uses of TNF-a antagonists. METHODS: A MEDLINE search (1966-March 2005) was conducted using the keywords "infliximab," "etanercept," "adalimumab," "TNF inhibitors," and "off-label" to identify published reports of off-label dermatologic uses of TNF-a inhibitors. RESULTS: Anti-TNF-a therapies have been reported in the following dermatologic diseases: sarcoidosis, hidradenitis suppuritiva, cicatricial pemphigoid, Behçet's disease, pyoderma gangrenosum, multicentric reticulohistiocytosis, apthous stomatitis, Sneddon-Wilkinson disease, SAPHO syndrome, pityriasis rubra pilaris, eosinophilic fasciitis, panniculitis, Crohn's disease, necrobiosis lipoidica diabeticorum, dermatomyositis, and scleroderma. The vast majority of these reports are in the form of individual case reports and small case series. Only two published randomized controlled trials involving the off-label use of a TNF inhibitor were found. CONCLUSIONS: A growing number of published reports suggest that anti-TNF-a therapies may be effective in the treatment of numerous inflammatory skin diseases outside their currently approved indications.

Adalimumab↗
PubMed2001

Extraintestinal manifestations of inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) may confront a variety of nonintestinal problems. The first North American population-based data describing the incidence rates of several of these disorders have been reported over the past year. Reports have also documented our expanding knowledge of peristomal pyoderma gangrenosum, and of ulcerative colitis following liver transplantation in patients with primary sclerosing cholangitis. Osteopenia continues to receive considerable attention. Factors such as osteoprotegrin ligand, and its interaction with receptor activator of nuclear factor kappa B, are connected with T-cell activity, inflammation, and osteoclastogenesis. Studies in these and other areas are addressed in this review.

Cholangitis, Sclerosing↗
PubMed2003

Extraintestinal complications of inflammatory bowel disease.

Recent studies of extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have demonstrated the importance of genetic predisposition in the etiology of musculoskeletal and cutaneous manifestations. In addition, small studies have shown infliximab to be effective in treating troublesome EIMs, particularly in pyoderma gangrenosum. Other trials have examined the safety of cyclooxygenase-2-specific nonsteroidal inflammatory drugs in IBD. Further work has been done on osteoporosis in IBD, and the American Gastroenterological Association has published a technical review and management guidelines for osteoporosis in a range of gastrointestinal disorders. However, despite further publications, debate remains concerning whether IBD patients with osteoporosis have a significant increase in fracture risk, and whether the bone loss is related to the disease or to its treatment.

Bone Diseases, Metabolic↗
PubMed2004

Management of extraintestinal manifestations and other complications of inflammatory bowel disease.

The past 18 months have seen many studies of the prevalence, pathogenesis, and treatment of the extraintestinal manifestations of inflammatory bowel disease (IBD). Inhibitors of tumor necrosis factor alpha have shown effectiveness in randomized trials for the treatment of spondyloarthropathies and ocular manifestations. Open-label studies suggest that these agents may be effective for pyoderma gangrenosum as well. The epidemiology of primary sclerosing cholangitis (PSC), and its relationship to IBD, is becoming clearer. Colorectal neoplasia in PSC remains an important clinical problem. Osteoporosis occurs more commonly in IBD, but the relative importance of corticosteroid use versus underlying chronic bowel inflammation as risk factors remains controversial. Chromoendoscopy may be an important means to improve detection of colorectal neoplasia in IBD. Observational studies suggest that prolonged use of aminosalicylates is associated with decreased risk of neoplasia, but data are conflicting. A randomized trial of ursodeoxycholic acid in PSC showed decreased risk of colorectal neoplasia in patients receiving the drug relative to those on placebo.

Arthritis↗
PubMed2005

Blau syndrome and related genetic disorders causing childhood arthritis.

Blau Syndrome (BS) is an inheritable disorder characterized by granulomatous polyarthritis, panuveitis, and exanthema. It was described by Edward Blau in 1985, the same year in which Douglas Jabs reported a very similar family. Clinically indistinguishable from early onset sarcoidosis (EOS), both are now known to share a mutated form of caspase recruitment domain-15 (CARD 15), a protein involved in activation of nuclear factor kappa B which is in turn an up-regulator of pro-inflammatory cytokine transcription. An association between BS and EOS was suspected for years given the striking similarities of the core triad (arthritis-uveitis-dermatitis) and a common emerging pattern of systemic involvement. Hence, the familial form (BS) and the sporadic form (EOS) are almost certainly the same illness/defect, inherited in the first and acquired in the second as a result in most cases of a de novo mutation. Another form of granulomatous arthritis with uveitis, Crohn's disease, has also been associated with mutations in CARD 15 (albeit at a different domain) and despite similar phenotypes there are obvious differences including gut inflammation and pyoderma gangrenosum in Crohn's disease. This paper will review the clinical characteristics of these three disorders and their association with mutations in the CARD 15 gene.

Adolescent↗
PubMed1976

Arthritis with an inflammatory dermatosis resembling Sweet's syndrome. Report of a unique case and review of the literature on arthritis associated with the inflammatory dermatoses.

A patient with a unique case of chronic episodic arthritis coincident with flares of acneform, pustular, nodular and ulcerating skin lesions was observed over a five-year period. This patient and a review of the literature on arthritis associated with the inflammatory dermatoses provide evidence which may interrelate several of these nosologically confusing skin conditions, e.g., the family of leukocytoclastic angiitides with the newly posited acute febrile neutrophilic dermatosis of Sweet. Systemic manifestations and a variety of acneform, pustular, nodular and ulcerating cutaneous lesions in the inflammatory dermatoses are best explained by small vessel involvement, with individual syndromes being determined by the type and degree of vascular change. Perivascular neutrophilic infiltration is the unifying histologic feature of these small vessel diseases. Neutrophil infiltration differentiates these entities, and our patient, from the histologically nonspecific inflammations of the skin, e.g., Behcet's disease and pyoderma gangrenosum, which, although capable of causing identically appearing skin lesions, consist predominantly of lymphocytic dermal infiltrates even in the earlier stages. It appears important to recognized these morphologically varied acute inflammatory dermatoses with perivascular neutrophilic infiltration in view of their systemic features and the dramatic efficacy of corticosteroid therapy.

Adult↗
PubMed1982

Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease.

A six year old female presented with a recent history of pyoderma gangrenosum involving her legs and arms associated with an episode of Mycoplasma-like pneumonia. This was followed by Aspergillus osteomyelitis involving her left ulna and right femur. Both the skin lesions and the osteomyelitis responded to prolonged treatment with antifungal and antibiotic agents. Investigation of this patient revealed (1) an elevated serum IgE (4,800 units/ml), (2) defect in neutrophil chemotaxis that appeared to be due to immune complexes, (3) an abnormal nitroblue tetrazolium (NBT) result (0 percent stimulated and unstimulated), and (4) depressed mitogen responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen, negative results of intradermal skin tests, and negative dinitrochlorobenzene (DNCB) sensitization. The patient's clinically unaffected sibling had similar findings except for a positive DNCB response. In both children, intracellular bacterial killing of catalase-positive and negative organisms was normal. Kindred studies revealed widespread T-cell abnormalities consistent with autosomal dominant inheritance. Tissue typing studies showed that affected siblings shared the A1, B8, DR3 haplotype. This kindred is unique in that both the proband and the sibling have abnormalities of both the hyper-IgE syndrome and chronic granulomatous disease.

Child↗
PubMed1990

Management of patients and side effects during cyclosporine therapy for cutaneous disorders.

Cyclosporine has been used in the experimental treatment of multiple inflammatory diseases of presumed autoimmune origin, including insulin-dependent diabetes mellitus, uveitis, rheumatoid arthritis, inflammatory bowel diseases, Graves' disease, and myasthenia gravis. In dermatology, the drug has been used successfully as primary therapy for psoriasis and psoriatic arthritis, alopecia areata, pyoderma gangrenosum, Behçet's disease, atopic dermatitis, and lichen planus. At a dose of 3 to 5 mg/kg per day, cyclosporine is well tolerated by most patients. However, because of concerns about its potential short- and long-term side effects, patients who use this drug require close monitoring. This review discusses appropriate clinical and laboratory evaluations, common and unusual side effects and their management, drugs that might alter the pharmacokinetics of cyclosporine metabolism, and criteria for dosage adjustments.

Cyclosporins↗
PubMed1995

Clofazimine: a review of its medical uses and mechanisms of action.

Clofazimine has been in clinical use for almost 40 years, but little is known of its mechanism of action. The primary indication for clofazimine is multibacillary leprosy, but it is useful in several infectious and noninfectious diseases, such as typical myocobacterial infections, rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe acne, pustular psoriasis, and discoid lupus erythematosus. Postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2. Clinical experience, possible mechanisms of action, and side effects of clofazimine are summarized.

Clofazimine↗
PubMed1995

[Leg ulcers in systemic diseases].

The collagen vascular diseases and vasculitis, in particular, are occasionally associated with chronic, relapsing lower extremity ulcerations. Different mechanisms can induce such ulcerations, and an understanding of the type of ulcerations is important in the differential diagnosis of patients with leg ulcerations in general, and management of these patients in particular. In this review, the authors analyze the various mechanisms of the leg ulcerations in these patients and their treatments: vasculitis, thrombosis, traumatisms, calcinosis, panniculitis, pyoderma gangrenosum, infections, and induced by treatments.

Connective Tissue Diseases↗
PubMed2005

A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder that primarily affects bone but is often accompanied by inflammation of the skin and/or gastrointestinal tract. The etiology is unknown but evidence suggests a genetic component to disease susceptibility. Although most cases of CRMO are sporadic, there is an autosomal recessive syndromic form of the disease, called Majeed syndrome, which is due to homozygous mutations in LPIN2. In addition, there is a phenotypically similar mouse, called cmo (chronic multifocal osteomyelitis) in which the disease is inherited as an autosomal recessive disorder. The cmo locus has been mapped to murine chromosome 18. In this report, we describe phenotypic abnormalities in the cmo mouse that include bone, cartilage and skin inflammation. Utilizing a backcross breeding strategy, we refined the cmo locus to a 1.3 Mb region on murine chromosome 18. Within the refined region was the gene pstpip2, which shares significant sequence homology to the PSTPIP1. Mutations in PSTPIP1 have been shown to cause the autoinflammatory disorder PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne). Mutation analysis, utilizing direct sequencing, revealed a single base pair change c.293T --> C in the pstpip2 gene resulting in a highly conserved leucine at amino acid 98 being replaced by a proline (L98P). No other mutations were found in the coding sequence of the remaining genes in the refined interval, although a 50 kb gap remains unexplored. These data suggest that mutations in pstpip2 may be the genetic explanation for the autoinflammatory phenotype seen in the cmo mouse.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Other uses of homologous skin grafts and skin bank bioproducts.

The main use of homologous skin grafts or grafts of related bioproducts is in the treatment of severe burns. However, various new clinical and experimental sectors, in which this type of skin substitute can be useful, have recently emerged. The main new clinical indications for skin allografts include: skin loss, surgical wounds and bullous diseases. In these fields donor skin can be used for different purposes: as a physiological biological dressing to control pain and protect deep structures such as tendons, bones, cartilage and nerves, and to promote reepithelization with a significant reduction in healing time, and as skin substitute with dermal tissue to guide repair and make it as physiological as possible. In particular, skin bank bioproducts are currently used in the treatment of several conditions such venous and arterial leg ulcers, pressure ulcers, diabetic foot ulcers, pyoderma gangrenosum, post traumatic lesions, Mohs surgery, reconstructive surgery, wound cover in critical areas, aesthetic surgery, congenital epidermolysis bullosa and Lyell's syndrome. Skin bank bioproducts have also been used for experimental indications, to study in vitro toxicology and in vitro skin biology. Recently the demonstration that de-epidermized dermis (DED) has all the characteristics of an excellent dermal substitute into which various types of cells can be introduced and made to develop, opens exciting new possibilities of research in the field of wound healing and tissue engineering. Our preliminary observations seems to indicate that CD 34+ stem cells from umbilical cord blood can survive in DED and in a few weeks populate collagen bundles. The observation of tubular structures without lumina close to collagen bundles as well as clusters of epithelioid or fibroblast-shaped cells may represent aspects of differentiation of CD 34+ stem cells. More detailed and sophisticated studies are clearly needed to answer all the questions that these initial observations pose. Anyway the 3-dimensional model proposed seems to be suitable for the study of the behaviour of peripheral CD 34+ and perhaps also other types of stem cells in 3-dimensional dermal matrix.

Humans↗