Pyoderma gangraenosum Erfolgreiche topische Therapie mit Tacrolimus (FK506)

Pyoderma gangrenosum is a distinct clinical entity characterized by chronic, recurring, destructive ulcerations. Although the pathogenesis of pyoderma gangrenosum is unknown, immunologic aberrations of neutrophil granulocytes seem to be important. Systemic steroids and macrolide lactones such as cyclosporin A and tacrolimus have been reported to be useful in the clinical management of disease. Pyoderma gangrenosum has been found to be associated with several systemic diseases.The association with chronic ulcerative colitis is well known, but the diagnosis may be complicated by early administration of systemic steroids.Therefore, local immunosuppression with topically applied agents could be an efficient therapeutic alternative especially for mild or early cutaneous lesions.We describe the successful topical treatment of a patient with multiple lesions of pyoderma gangrenosum with 0,1% tacrolimus (FK506) ointment which is known to have better dermal penetration and higher immunosuppressive potency than topical cyclosporin A. In addition, other indications for topical tacrolimus are discussed.     

Management of pyoderma gangrenosum--an update

Pyoderma gangrenosum is a neutrophilic dermatosis with distinctive clinical manifestations. It is frequently associated with systemic diseases like inflammatory bowel disease, rheumatoid arthritis and myeloproliferative diseases. The etiopathogenesis of pyoderma gangrenosum is still not well understood. Clinically it is classified into ulcerative, pustular, bullous and vegetative types. The diagnosis mainly depends on the recognition of evolving clinical features as there are no specific investigations for the diagnosis. It is essential to exclude other infectious diseases before therapy is initiated as corticosteroids and immunosuppressant therapy are the mainstays in the treatment of this disease. Recently, drugs like tacrolimus, mycophenolate mofetil and infliximab have shown promising results in this condition. Recent concepts regarding the various types of pyoderma gangrenosum and its management are reviewed.     

Efficacy and safety of etanercept for postoperative pyoderma gangrenosum after infliximab serum sickness

Non‐peristomal postoperative pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that occurs in the early postoperative period at surgical incisions, most commonly after breast surgery. Early diagnosis and treatment is essential to prevent severe scaring. TNF‐alpha inhibitor infliximab was reported to be efficient in treatment of PPG refractory to systemic corticosteroids. However infliximab can be not well tolerated. We report the first case of etanercept efficacy in post‐plastic breast surgery pyoderma gangrenosum after infliximab serum sickness.     

Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome

Infliximab, a chimeric antitumor necrosis factor alpha monoclonal antibody (anti-TNF alpha), has been recently shown to have a beneficial effect on pyoderma gangrenosum associated with inflammatory bowel disease. Patients with the syndromic triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne, an autoinflammatory process caused by mutations in the CD2 binding protein-1 (CD2BP1) gene, can have severe pyoderma gangrenosum. We describe a 14-year-old patient with this syndrome who was unresponsive to multiple therapies. A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome.     

Genital pyoderma gangrenosum: Report of two cases and published work review of Japanese cases

Pyoderma gangrenosum is an ulcerative skin disorder showing characteristic non‐infectious ulcers and affects the lower extremities in approximately 70% of cases. Pyoderma gangrenosum is commonly associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Herein, we report two cases of Japanese patients diagnosed with genital pyoderma gangrenosum. Case 1 was a 74‐year‐old woman without associated systemic complications, whose skin lesion resembled a squamous cell carcinoma and was limited to the vulva. Case 2 is an 89‐year‐old man, who suffered from myelodysplastic syndrome and acute myeloid leukemia, and presented with penile and leg ulcers mimicking pressure sores. Both cases responded well to systemic steroids. We review 13 genital pyoderma gangrenosum cases (76.9% male; aged 30–89 years) from 1996 to 2012 in Japan, including 11 previously reported cases and the present study's two cases. Four of the 13 genital pyoderma gangrenosum cases had associated systemic diseases and their skin lesions spread to the extragenital areas. Eight of the remaining nine genitalia‐localized pyoderma gangrenosum cases had no associated systemic diseases. In conclusion, genital pyoderma gangrenosum is rare and may be misdiagnosed. It should therefore be considered in cases of refractory genital ulcers. In addition, genitalia‐localized pyoderma gangrenosum tends to be without systemic complications.     

Improvement of Pyoderma gangrenosum and psoriasis associated with Crohn disease with anti-tumor necrosis factor alpha monoclonal antibody.

BACKGROUND: Infliximab is an anti-tumor necrosis factor alpha monoclonal antibody IgG effective in the treatment and maintenance of remission of active refractory Crohn disease and associated draining enterocutaneous fistulae. Multiple infusions of infliximab show promising results in patients with rheumatoid arthritis. Currently, there is limited clinical experience with infliximab, and no published reports exist on its use in cutaneous disorders. OBSERVATIONS: We describe 2 patients with Crohn disease and pyoderma gangrenosum and 1 patient with Crohn disease and psoriasis who were treated with infliximab for recalcitrant Crohn fistulae, with concurrent improvement in their skin diseases. CONCLUSIONS: These cases suggest that infliximab, a promising therapeutic agent for refractory Crohn disease and fistulae, may also be effective in the treatment of pyoderma gangrenosum and psoriasis associated with Crohn disease.     

Use of infliximab in pyoderma gangrenosum

A 57-year-old man, with a 2-year history of Crohn's disease, presented with a rapidly progressive abdominal ulcer. It was clinically and histologically consistent with pyoderma gangrenosum but it did not respond to either high-dose oral prednisolone or intravenous hydrocortisone. Infliximab resulted in an early, dramatic and sustained improvement. His bowel symptoms, which flared a few weeks prior to the onset of pyoderma gangrenosum, only partially improved. Despite six infliximab infusions, the inflammatory bowel disease is poorly controlled, whereas the pyoderma gangrenosum remains healed.     

Pyoderma gangrenosum complicated by herpes simplex virus infection

High-dose immunosuppression used in the treatment of pyoderma gangrenosum predisposes patients to opportunistic infections. A 66-year-old man presented with recalcitrant pyoderma gangrenosum in which the ulcer itself became infected with herpes simplex virus type 1. This patient was immunosuppressed with multiple agents including topical and oral corticosteroids, cyclosporin, mycophenolate mofetil, intravenous immunoglobulin and infliximab. However, the patient's ulcer continued to extend despite this. It was not until the presence of this virus was detected using polymerase chain reaction on a viral swab of the lesion and oral aciclovir was commenced that the ulcer began to heal. In addition, a fungal granuloma developed on this patient's left forearm as a complication of the potent immunosuppression, which was resolved following treatment with oral voriconazole.     

Multiple cavitary pulmonary nodules in association with pyoderma gangrenosum: case report

Pyoderma gangrenosum is a rare neutrophilic disease of unknown origin that is associated with systemic diseases in 50% of cases. It is characterized by erythematous-violaceous nodular lesions that quickly progress to painful ulcers, with undermined edges, necrotic-hemorrhagic, varying in size and depth, located mainly in the lower limbs. Extracutaneous locations of pyoderma gangrenosum are rare, usually involving the lungs; the main differential diagnosis in these cases is Wegener granulomatosis. We report a case of pyoderma gangrenosum, which showed multiple cavitary lung nodules, with good response to high doses of steroids. Once excluded the possibility of Wegener granulomatosis, the authors concluded that it was the manifestation of systemic pyoderma gangrenosum with pulmonary involvement.     

Pyoderma gangrenosum on the breast: A case presentation and review of the published work

We present a case of pyoderma gangrenosum localized on the breast, without a preceding surgical intervention and associated systemic disorder. The ulcer had rapidly developed and covered a large portion of the breast. The patient responded well to systemic steroids and salicylazosulfapyridine and the ulcer completely healed with scarring after 3 months of treatment. Pyoderma gangrenosum rarely involves the breasts. A published work survey disclosed only 31 reported cases up to date. In most of these cases the lesions were related to previous surgical interventions, probably as the result of a pathergy phenomenon. The main differential diagnoses were skin and soft tissue infections including necrotizing fasciitis, and malignant neoplasms. Negative initial wound cultures and the relative sparing of nipple/areola complex helped to eliminate these disorders. Though an unusual site for pyoderma gangrenosum, lesions on the breast showed the characteristic clinical features of the disease. The types of associated disorders were also similar to those of the cases with classical pyoderma gangrenosum. As most of the lesions healed with significant scarring, early recognition and treatment of pyoderma gangrenosum located on the breast is important to prevent serious physical and psychological morbidity.     

Systemic ciclosporin and tacrolimus in dermatology

Ciclosporin and tacrolimus are calcineurin inhibiting immunosuppressant agents useful in the treatment of immune-mediated inflammatory dermatoses. Available data and clinical experience demonstrate ciclosporin's efficacy in treating psoriasis, atopic dermatitis, pyoderma gangrenosum, lichen planus, autoimmune bullous disease (in combination with corticosteroids), recalcitrant chronic idiopathic urticaria, and chronic dermatitis of the hands and feet. Although the role of topical tacrolimus in atopic dermatitis is well established, such experience with the oral formulation of tacrolimus has been limited. However, there are several case studies and anecdotal reports of the successful use of oral tacrolimus in various dermatoses. In this article we discuss the utility of systemic ciclosporin and tacrolimus in dermatology.     

Pyoderma gangrenosum associated with ulceratlve colitis-first case report from Nepal

A case of pyoderma gangrenosum with ulcerative colitis from Nepal is reported. The patient responded well to a combination of oral steroids, clofazimine. dapsone and salazopyrine within a period of 3 months.     

Refractory pyoderma gangrenosum treated with infliximab in an infant

We report the case of an 11‐month‐old boy with severe recalcitrant pyoderma gangrenosum refractory to prednisone, dapsone and ciclosporin. Treatment with infliximab was well tolerated, and resulted in an excellent clinical response that has been sustained for 15 months. The characteristics of this condition in children and the use of infliximab in infants are both reviewed.     

Rare association of pyoderma gangrenosum and palmoplantar pustulosis: A case report and review of the previous works

Pyoderma gangrenosum is a rare inflammatory, ulcerative skin disease that mainly involves the lower extremities. It frequently occurs in association with systemic diseases such as inflammatory bowel disease, myeloproliferative disorders and rheumatoid arthritis. Palmoplantar pustulosis is also an inflammatory dermatosis characterized by recurrent sterile pustules localized on the palms and soles. These two dermatoses are histologically characterized by neutrophilic infiltration into the lesional skin. Co‐occurrence of pyoderma gangrenosum and palmoplantar pustulosis in a single patient is extremely rare. We report a case of pyoderma gangrenosum occurred in a patient with palmoplantar pustulosis, with a review of the previously reported cases. A 68‐year‐old Japanese woman with a 10‐year history of palmoplantar pustulosis developed a skin ulcer on the left lower leg. The ulcer was diagnosed as pyoderma gangrenosum based on the clinical and histological findings, and rapidly improved in response to oral prednisolone. In addition to our case, five cases with palmoplantar pustulosis who developed pyoderma gangrenosum have been reported. These cases were thought to have some characteristics in common, such as marked female predominance, no association with inflammatory bowel disease and myeloproliferative disorders, and good response to less aggressive therapy. The co‐occurrence of pyoderma gangrenosum and palmoplantar pustulosis in our case may have an etiological link, rather than being a coincidental complication.     

Infliximab for the treatment of disseminated pyoderma gangrenosum associated with ulcerative colitis. Case report and literature review

We report the case of a 19-year-old woman who developed an acute disseminated pyoderma gangrenosum (PG) during a severe flare of ulcerative colitis (UC). She was successfully treated with a 3-dose regimen of the anti-tumor-necrosis-factor-alpha antibody infliximab. The literature on the effectiveness of this biological agent was reviewed, including 8 other cases of UC-associated PG and 77 cases of Crohn's-disease-associated PG. This case report and the review of the literature demonstrate that infliximab can be successfully used to treat patients with PG associated with inflammatory bowel diseases.     

Infliximab for peristomal pyoderma gangrenosum

Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG) that is more refractory to treatment. It is a cause of severe morbidity and poses a therapeutic challenge for the clinician. Infliximab (Remicade(R); Centocor, Malvern, PA, USA) is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been proven to be effective in the treatment of inflammatory bowel disease (IBD) and rheumatoid arthritis. Currently, very few reports exist documenting its use in the treatment of PG and none in the treatment of PPG. We describe our experience of treating three patients with IBD-associated PPG with infliximab. All patients tolerated the drug without significant side-effects. Two patients with PPG recovered completely following the administration of infliximab, and one patient had a partial response to the drug. We conclude that infliximab appears to be a safe and effective therapeutic alternative in patients with PPG.     

Piodermas gangrenosos eruptivos asociados al consumo de cocaína inhalada. Presentación de dos casos

We present the cases of 2 regular cocaine users aged 30 and 37 years who developed a cutaneous condition with an identical presentation and a similar clinical course. The lesions first appeared as eruptions on the back and then spread to other parts of the body. They consisted of painful inflammatory nodules that developed into abscesses and ulcers that grew outwards. They had a granulomatous base and irregular violaceous edges. The results of histopathologic studies were compatible with the clinical diagnosis of pyoderma gangrenosum, and additional tests ruled out underlying diseases. After several therapeutic failures with usual treatments, the patients responded quickly to infliximab after interrupting their cocaine consumption. The association between pyoderma gangrenosum and cocaine use was clear as both suffered clinical relapses at the same time as they started using the drug again.     

A case of vulvar pyoderma gangrenosum associated with collagenous colitis

Pyoderma gangrenosum is a reactive inflammatory dermatosis which belongs to the spectrum of neutrophilic dermatoses. Due to a lack of diagnostic criteria, pyoderma gangrenosum is mainly a diagnosis of exclusion. It is rarely observed on the perineum, and vulvar involvement is even less frequent. Collagenous colitis is an idiopathic inflammatory colonic disease that is included in the microscopic colitides. The colonic mucosa and the crypt architecture are preserved but histologic alterations are found. We describe a case of collagenous colitis associated with vulvar pyoderma gangrenosum that improved spectacularly with cyclosporine 3 mg/kg/day and the twice-daily application of topical tacrolimus 0.1%.     

Multifocal and refractory pyoderma gangrenosum: Possible role of cocaine abuse

Pyoderma gangrenosum is a rare and severe inflammatory skin condition. There are different variants, including generalised and atypical forms, but the most common presentation is an enlarging ulcer on the lower extremities. Treatment can represent a challenge for physicians and there are no guidelines based on randomised controlled trials. We report an exceptional case of widespread and refractory pyoderma gangrenosum in a middle‐aged woman where cocaine use may have played a role. Treatment with i.v. pulse corticosteroids and cyclosporine was ineffective, and disease control was obtained with oral corticosteroids together with mycophenolic acid, infliximab and abstinence from cocaine consumption. There was a temporal relationship between disease outbreaks and cocaine consumption and improvement after its discontinuation. In the present case such clinical severity without associated pathology and the temporal association with cocaine abuse raises the possibility of cocaine playing an aetiological role as well as accounting for therapy resistance.     

Pyoderma gangrenosum associated with biphenotypic acute leukemia

Pyoderma gangrenosum is a neutrophilic dermatosis that may be associated with myeloid malignancies. Less information is available about the association of pyoderma gangrenosum with lymphoid malignancies. We present, to our knowledge, the first case of pyoderma gangrenosum associated with biphenotypic acute leukemia wherein the malignant cells show a phenotype specific for myelogenic and lymphocytic leukemia. Histopathologic examination revealed rather nonspecific features without involvement of leukemic cells in the skin lesions. Treatment with systemic steroids was followed by characteristically rapid healing of the skin lesion.