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PubMed2003

Causes, investigation and treatment of leg ulceration.

Chronic ulceration of the lower leg is a frequent condition, with a prevalence of 3-5% in the population over 65 years of age. The incidence of ulceration is rising as a result of the ageing population and increased risk factors for atherosclerotic occlusion such as smoking, obesity and diabetes. Ulcers can be defined as wounds with a 'full thickness depth' and a 'slow healing tendency'. In general, the slow healing tendency is not simply explained by depth and size, but caused by an underlying pathogenetic factor that needs to be removed to induce healing. The main causes are venous valve insufficiency, lower extremity arterial disease and diabetes. Less frequent conditions are infection, vasculitis, skin malignancies and ulcerating skin diseases such as pyoderma gangrenosum. But even rarer conditions exist, such as the recently discovered combination of vasculitis and hypercoagulability. For a proper treatment of patients with leg ulcers, it is important to be aware of the large differential diagnosis of leg ulceration.

Arterial Occlusive Diseases↗
PubMed2000

Topical tacrolimus in dermatology.

Tacrolimus and cyclosporin A are potent immunosuppressants that are used systemically to treat several inflammatory skin conditions successfully. They differ in their structure and tacrolimus is 10-100 times more potent than cyclosporin A. They have similar side-effects. They have been used topically in various clinical studies. Topical cyclosporin A is largely ineffective whereas topical tacrolimus is effective in treating atopic dermatitis. Topical tacrolimus has not been studied sufficiently in treating psoriasis although it has been used successfully in allergic contact dermatitis, erosive mucosal lichen planus and pyoderma gangrenosum.

Adult↗
PubMed2000

Topical sucralfate in the management of peristomal skin disease: an open study.

Dermatoses affecting the skin around stoma sites are common and difficult to treat. We have investigated the effectiveness of topical sucralfate in the management of peristomal dermatoses in adults using an open study design. Apart from forming a physical barrier to further irritation, sucralfate binds to basic fibroblast growth factor preventing its degradation and thereby promotes healing. In eight out of nine patients with faecal or urine erosions, daily, topical sucralfate treatment was associated with healing within 4 weeks. There was limited or no response to treatment in a further nine patients with traumatic ulcers, excoriated dermatitis or pyoderma gangrenosum. Topical sucralfate represents a safe, inexpensive and effective therapeutic intervention, particularly for those patients with high output or short stomas where repeated stoma leakage may be unavoidable.

Abdomen↗
PubMed2002

Cytokine blocking agents in dermatology.

Cytokines are intercellular messengers that have an important role in the development and maintenance of cutaneous inflammation. The primacy of cytokines in eliciting cutaneous immune responses makes them a highly attractive target for new biological response modifiers. Targeting of cytokines is still in its infancy for therapy of skin disease. However, blocking tumour necrosis factor alpha by infliximab or etanercept has shown particular promise, especially in the management of psoriasis. Anecdotally, this approach is also effective for a variety of dermatological conditions including pyoderma gangrenosum and Behçet's syndrome. We review the current and prospective roles of cytokine blocking agents in the treatment of skin disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Necrotizing eosinophilic folliculitis as a manifestation of the atopic diathesis.

BACKGROUND: Eosinophilic folliculitis (EF) is an idiopathic eruption of sterile pustules and papules involving the trunk, face, and extremities, associated in many cases with human immunodeficiency virus (HIV) infection. The classic histopathology is one of follicular-based, eosinophilic spongiosis with variable microabscess formation. We describe nine HIV-negative patients who manifested a novel form of pustular EF in the setting of atopy. MATERIALS AND METHODS: Paraffin sections of skin biopsies from ten patients, stained with hematoxylin and eosin and special preparations to evaluate for microbial pathogens, were examined. Detailed clinical histories and serologic studies were obtained. RESULTS: Among the clinical presentations in seven men, two women, and one girl (age range, 11-62 years) were ulcerative and/or nodular plaques mainly on the face and/or extremities, sometimes in an annular configuration. The clinical considerations included deep mycotic infection, ulcerative herpes, systemic vasculitis, Mucha Haberman disease, and pyoderma gangrenosum. All patients had a personal and/or family history of atopy. Co-existent medical illnesses included psoriasis, lupus erythematosus, and lymphoproliferative disease. One patient was on a calcium channel blocker, one on multiple antidepressants, and two on antihistamines, all of which are associated with immune dysregulation. All skin biopsies showed variable intra- follicular eosinophilic microabscesses, follicular necrosis, folliculocentric necrotizing eosinophilic vasculitis, marked degeneration of connective tissue fiber elements, and striking tissue eosinophilia, including flame figure formation and dermal eosinophilic abscesses. Apart from commensals, such as Pityrosporum and Demodex, microbial pathogens were not identified. CONCLUSIONS: The presentations differed from conventional EF by virtue of a strong association with atopy and by the presence of ulceration, nodule formation, follicular and dermal necrosis, and eosinophilic vasculitis. We propose the term "necrotizing eosinophilic folliculitis," and suggest that the basis of this novel form of EF is an unrepressed T-helper lymphocyte type 2 (Th2)-dominant response to various epicutaneous stimuli in patients with atopy, the prototypic immune dysregulatory state associated with a Th2-dominant cytokine milieu.

Adult↗
PubMed2002

Cutaneous involvement of dermatomyositis can respond to Dapsone therapy.

BACKGROUND: Dapsone (4,4-diaminodiphenylsulfone) is a sulfone antibiotic used in the treatment of leprosy, but dermatologists more commonly utilize its anti-inflammatory properties particularly directed against leukocytes to treat various bullous disorders, erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, cutaneous vasculitis, and cutaneous forms of lupus erythematosus. The cutaneous manifestations of dermatomyositis are often resistant to antimalarial and immunosuppressive therapies. METHODS: Two patients with cutaneous dermatomyositis unresponsive to combination therapy with prednisone, hydroxychloroquine, quinacrine, and immunosuppressive medications had Dapsone added to their therapy. RESULTS: Both patients showed rapid improvement with the addition of Dapsone. Each had an exacerbation of their cutaneous dermatomyositis on Dapsone with withdrawal and subsequent improvement when the Dapsone was reinstituted. CONCLUSIONS: Dapsone therapy for cutaneous dermatomyositis may have a wider role in treatment for these patients refractory to prednisone and antimalarial therapy.

Adult↗
PubMed2002

Anogenital and buttock ulceration in infancy.

Rashes in the anogenital and buttock region are some of the commonest dermatological problems occurring in infancy. The most frequent causes seen in clinical practice are ulcerating haemangiomas, bullous impetigo and severe irritant contact dermatitis. Other causes include nutritional deficiencies, bullous diseases, trauma, Langerhans cell histiocytoses and inflammatory disorders such as pyoderma gangrenosum and Crohn's disease. This review presents a brief overview of these causes and outlines the recommended management strategies.

Buttocks↗
PubMed2002

Tacrolimus: a review of its use for the management of dermatoses.

The newly developed immunomodulator tacrolimus (FK506) is the first of a new class of agents that have enormous potential to change the way that dermatoses are treated and managed. Tacrolimus has been found to be active in a topical formulation with the latter exerting its effects by acting on the signal transduction pathways inside T cells and inhibiting gene transcription. The result is decreased responsiveness of T cells to antigens. Percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin and, therefore, the drug will be taken in at progressively lower quantities as lesions heal. There is limited systemic absorption of tacrolimus over the course of therapy. The most extensive experience with tacrolimus has been in treating atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to be effective in reducing the symptoms and severity of atopic dermatitis in adults and the paediatric population. Furthermore, there have been no significant toxic effects associated with topical therapy with tacrolimus. The most common complaint is that of local irritation after applying the ointment. This is generally transient and the patient is able to continue with therapy. The other dermatoses where tacrolimus has been used include contact dermatitis, psoriasis and pyoderma gangrenosum.

Administration, Oral↗
PubMed1999

Thalidomide increases human keratinocyte migration and proliferation.

Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

Cell Division↗
PubMed2001

Topical tacrolimus and pimecrolimus: future directions.

Topical tacrolimus ointment and pimecrolimus cream represent the first members of a new class of medications. Topical immunomodulators have been developed for the treatment of atopic dermatitis. Their superb safety profiles and excellent efficacy as anti-inflammatory agents make them attractive candidates to treat a host of other skin disorders. This article reviews published experiences that use them for psoriasis, seborrheic dermatitis, lichen planus, pyoderma gangrenosum and other diseases. Possible modifications to these compounds and novel untested applications are discussed.

Administration, Cutaneous↗
PubMed2001

Tacrolimus clinical studies for atopic dermatitis and other conditions.

The first topical immunomodulator approved for human use, tacrolimus ointment (Protopic, Fujisawa, Healthcare, Inc, Deerfield, IL), has been shown to be effective and safe in the treatment of children (aged 2 years and older) and adults with atopic dermatitis (AD). Clinical trials conducted worldwide have involved 12,000 patients, with safety and efficacy data available for up to 3 years of treatment. In addition to its beneficial effects in the management of AD, topical tacrolimus has also been reported to be of benefit in other immunologically mediated skin diseases including: hand dermatitis, contact dermatitis, eyelid dermatitis, erosive lichen planus, steroid-induced rosacea, pyoderma gangrenosum, and graft-versus-host disease. This article reviews the clinical experience of topical tacrolimus in the treatment of AD and other skin conditions.

Administration, Cutaneous↗
PubMed2000

Treatment of chronic plaque-stage psoriasis and psoriatic arthritis with mycophenolate mofetil.

Mycophenolate mofetil (MMF), a widely used immunosuppressant in organ transplantation, is a recent addition to the therapeutic armamentarium of autoimmune and inflammatory skin disorders in dermatology. We describe 5 patients with moderate to severe chronic plaque psoriasis and 6 patients with psoriatic arthritis that was refractory to conventional systemic and/or topical antipsoriatic treatment who were treated with MMF monotherapy (2 g/d) in a 10-week study. Although MMF was tolerated well in all patients, only patients with moderate psoriasis and psoriatic arthritis improved with therapy, whereas patients with severe psoriasis did not respond to MMF. Although MMF seems to be effective and safe for blistering autoimmune diseases and pyoderma gangrenosum, our data do not allow optimistic statements on the use of MMF in severe plaque-stage psoriasis. However, MMF may develop into an interesting therapeutic alternative for patients with psoriatic arthritis.

Adult↗
PubMed2000

Peristomal dermatoses: a novel indication for topical steroid lotions.

BACKGROUND: Dermatoses that interfere with the normal use of a stoma appliance are common. When preventable causes, such as infection or allergy, are not identified, barrier preparations or topical steroids have been used. However, topical medicaments formulated in a cream or ointment base will cause stoma bags to detach, resulting in leaks. OBJECTIVE: Our purpose was to investigate the efficacy and suitability of corticosteroids in aqueous/alcohol lotions in the management of peristomal dermatoses. METHODS: A clinic run by a dermatologist and 2 stoma nurses was created. Patients with a variety of noninfective, inflammatory dermatoses were treated with topical corticosteroid lotions up to a maximum of 4 weeks, with occasional use thereafter in some cases. RESULTS: Topical, aqueous/alcohol, corticosteroid lotions have been used in 60 patients and have proved particularly useful for the treatment of irritant dermatitis, pyoderma gangrenosum, psoriasis, and constitutional eczema. After the initial treatment course, occasional applications, approximately every 2 weeks, may be necessary to control the skin disorder. This low frequency of application minimizes the risk of side effects so that we have not identified local or systemic side effects in any of the patients treated so far. CONCLUSION: Topical corticosteroids formulated in aqueous alcohol lotion are effective and acceptable treatments for peristomal dermatoses. If used appropriately, the risk of side effects is low.

Administration, Topical↗
PubMed2003

Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.

Pyrin, the familial Mediterranean fever protein, is found in association with the cytoskeleton in myeloid/monocytic cells and modulates IL-1beta processing, NF-kappaB activation, and apoptosis. These effects are mediated in part through cognate interactions with the adaptor protein ASC, which shares an N-terminal motif with pyrin. We sought additional upstream regulators of inflammation by using pyrin as the bait in yeast two-hybrid assays. We now show that proline serine threonine phosphatase-interacting protein [PSTPIP1, or CD2-binding protein 1 (CD2BP1)], a tyrosine-phosphorylated protein involved in cytoskeletal organization, also interacts with pyrin. Recently, PSTPIP1/CD2BP1 mutations were shown to cause the syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA), a dominantly inherited autoinflammatory disorder mediated predominantly by granulocytes. Endogenous PSTPIP1/CD2BP1 and pyrin are coexpressed in monocytes and granulocytes and can be coimmunoprecipitated from THP-1 cells. The B box segment of pyrin was necessary and the B box/coiled-coil segment sufficient for this interaction, whereas the SH3 and coiled-coil domains of PSTPIP1/CD2BP1 were both necessary, but neither was sufficient, for pyrin binding. The Y344F PSTPIP1/CD2BP1 mutation, which blocks tyrosine phosphorylation, was associated with a marked reduction in pyrin binding in pervanadate-treated cells. PAPA-associated A230T and E250Q PSTPIP1/CD2BP1 mutations markedly increased pyrin binding as assayed by immunoprecipitation and, relative to WT, these mutants were hyperphosphorylated when coexpressed with c-Abl kinase. Consistent with the hypothesis that these mutations exert a dominant-negative effect on the previously reported activity of pyrin, we found increased IL-1beta production by peripheral blood leukocytes from a clinically active PAPA patient with the A230T PSTPIP1/CD2BP1 mutation and in cell lines transfected with both PAPA-associated mutants.

Cell Cycle Proteins↗
PubMed2000

Therapy: Hyperbaric Oxygen as the Only Effective Treatment in Mutilating and Resistant Systemic Vasculitis.

A forty year old man was seen in 1984 with a four year history of a painful vasculitis that responded transiently to plasma exchange. Diagnosis was revised to atypical pyoderma gangrenosum with further temporary benefit from lamprene and continuing maximally tolerated corticosteroids. The course fluctuated over the next ten years with gradual and increasing soft-tissue damage coupled with superimposed skin infections. A variety of organisms were isolated from the ulcerated areas, with each episode successfully managed on the basis of local debridement and appropriate antibiotic administration. In 1995, with extending skin devascularization, infectious bacterial episodes became more frequent and deep non-healing ulcers led to constant pain with virtual incapacity. In response to protocol hyperbaric oxygen therapy there was immediate reversal of the cutaneous damage, granulation tissue formed and new skin grew to cover the previous extensive deficits. As the lesions in his hands and feet improved so did his quality of life, with the patient again becoming ambulant and returning to work. Vascular access had become a major problem, and venography showed extensive occlusion with collateral circulation. A standard Hickman catheter was placed through the femoral vein into the inferior vena cava and functioned well over the next five years. At the end of 1996 the patient was admitted with an acute chest pain that was complicated by a major pulmonary embolus, from which he could not be resuscitated. This anecdotal experience demonstrates the important but underutilised benefits of hyperbaric oxygen in managing refractory, painful and penetrating skin ulcers. The cost of obtaining wound healing with reduction in pain by this form of treatment was approximately one-fifth of expenditure on previously ineffective management.

Journal Article↗
PubMed2002

Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

Autoimmune paraneoplastic syndromes are commonly encountered in patients with myelodysplastic syndromes (MDS). A review of case reports and small series suggest as many as 10% of MDS patients may experience various autoimmune syndromes. Clinical manifestations of such phenomena may include an acute systemic vasculitic syndrome, skin vasculitis, fever, arthritis, pulmonary infiltrates, peripheral polyneuropathy, inflammatory bowel disease, glomerulonephritis, and even classical connective tissue disorders, such as relapsing polychondritis. On the other hand, asymptomatic immunologic abnormalities have also been reported in these patients. These autoimmune manifestations frequently respond to immunosuppressive agents including steroids and occasional hematologic responses to steroid therapy have also been reported. We report five patients with history of MDS who manifested different spectrums of autoimmune phenomena including: pyoderma gangrenosum (PG), vasculitis, Coombs negative hemolytic anemia, idiopathic thrombocytopenia, and chronic inflammatory demyelinating polyneuropathy (CIDP). We also review the incidence, nature, course and response to therapy of these manifestations and discuss potential pathogenic mechanisms.

Adult↗
PubMedDate not supplied

[An unusual complication of bronchitis: Sweet's syndrome].

Sweet's syndrome (acute febrile neutophilic deromatosis) is a rare but not exceptional disease. Its first description was done in 1964, and its diagnosis is now well defined. A few days after a common upper respiratory infection, out patient presented erythematous plaques on the head, neck and forearms, with fever and general malaise. A skin biopsy showed a neutrophilic infiltrate. Oral steroids were prescribed, and healing occured within 48 hours. Respiratory and gastointestinal infections are frequently associated with Sweet's syndrom. Other associations have been described: neoplasias (mainly hemoproliferative diseases), inflammatory diseases, pregnancy, drugs. Cases classified as 'idiopathic' need a close follow-up: Sweet's syndrome may announce a malignant disease. There are also intermediate forms with other neutrophilic dermatoses, e.g. pyoderma gangrenosum.

Anti-Inflammatory Agents↗
PubMed2006

Emergence of Legionella pneumophila pneumonia in patients receiving tumor necrosis factor-alpha antagonists.

BACKGROUND: Patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy. METHODS: A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-alpha antagonists was compared with the rate in France overall. RESULTS: We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40-69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-alpha antagonist treatment at onset of infection was 38.5 weeks (range, 3-73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-alpha antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. CONCLUSIONS: L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti-TNF-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.

Adalimumab↗