Anti-tumor necrosis factor alpha monoclonal antibody (infliximab) for the treatment of Pyoderma gangrenosum associated with Crohn's disease

Here we report a case of Pyoderma gangrenosum (PG) associated with Crohn's disease successfully treated with infliximab. The efficacy of this drug in many inflammatory diseases has already been reported, but its use in PG has only been seen in very few cases. Our study confirms that this therapy is a valid alternative solution for treating PG, which is often unresponsive to conventional therapies.     

Etanercept: effective in the management of hidradenitis suppurativa

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic suppurative condition which is poorly responsive to treatment and is characterized by significant morbidity. Successful treatment of HS in patients treated with infliximab for concomitant Crohn's disease has been reported. More recent reports of positive responses to infliximab [an antitumour necrosis factor (TNF)-alpha agent] in patients who have HS but not Crohn's disease are encouraging. OBJECTIVES: TNF-alpha is implicated in many inflammatory disorders and we wished to determine the efficacy of subcutaneous etanercept, a competitive inhibitor of TNF-alpha in the control of HS symptoms. METHODS: We commenced six patients with severe, recalcitrant HS on etanercept (25 mg subcutaneously twice weekly in all cases). All patients had a normal chest X-ray and negative purified protein derivative test prior to treatment and were closely monitored throughout the treatment period for signs of infection. Patients self-assessed their disease activity and completed Dermatology Life Quality Index (DLQI) questionnaires immediately before the introduction of therapy and 24 weeks later in the case of four patients, and 12 weeks later in the case of two others. All patients were asked to estimate the time lapse between commencement of treatment and initial response. RESULTS: Treatment was well tolerated by all patients with no reported adverse reactions. A marked reduction in self-reported disease activity (mean reduction of 61% at 24 weeks), in DLQI scores (mean reduction of 64% at 24 weeks) and in relapse rates occurred. All patients rated etanercept as their most effective treatment to date. CONCLUSIONS: Our results show the effectiveness of etanercept in this group of patients with particularly challenging disease. Etanercept, unlike infliximab, may be administered subcutaneously, rendering costly day-case admissions unnecessary.     

Pyoderma gangrenosum – rebel without a cure?

Background Pyoderma gangrenosum (PG) is a rare neutrophilic, ulcerating dermatosis that is frequently difficult to diagnose and often a diagnosis of exclusion. It is hypothesized that PG may be caused by an abnormal T‐cell and neutrophil response, which correlates with its common link to other disorders, such as inflammatory bowel disease, rheumatoid arthritis, and malignancies. Several treatments have been used successfully for PG, but none has proven to be universally effective. Methods We present three cases of PG treated with adalimumab after failed courses of steroids (orally and parenterally), thalidomide, cyclosporine, and mycophenolate mofetil. Results Patients 2 and 3, who had previously responded to infliximab, albeit with recurrence, were successfully treated with adalimumab at a dose of 40 mg once a week. Patient 1 initially responded to adalimumab, but after 7.5 months failed to show wound bed improvement at a dose of 80 mg/week subcutaneously. This patient had not previously been treated with infliximab. Conclusion We believe adalimumab to be a valuable alternative for the treatment of PG, with comparable efficacy to infliximab.     

Mycobacterium marinum infection complicating Crohn's disease, treated with infliximab

Tumour necrosis factor-alpha inhibitors including infliximab are often used to treat a number of recalcitrant medical conditions. These agents are increasingly associated with infections, particularly mycobacterial infections. We report sporotrichoid spread of Mycobacterium marinum in a 37-year-old woman with Crohn's disease, who had been receiving infliximab infusions for 2 years. An infection had spread up the right leg, after she had been swimming on holiday in the Canary Islands. M. marinum was cultured from the lesions and also identified by PCR on formalin-fixed tissue. To our knowledge, this is the first report of M. marinum occurring in a patient receiving infliximab.     

Infliximab for treatment of resistant pyoderma gangrenosum associated with Crohn's disease

We present the case of an 18-year-old woman with Crohn's disease manifested by diffuse abdominal pain, bloody diarrhea accompanied by arthralgia, and swelling of large joints. On the lateral aspect of her right ankle there was an hemorrhagic, necrotic bullous lesion measuring 3 x 4 cm, surrounded by cutaneous inflammation and erythema. Biopsy showed a neutrophilic abscess-like ulcerative skin inflammation, which was diagnosed as pyoderma gangrenosum. The patient was treated with high doses of parenteral methylprednisolone, but her condition failed to improve and infliximab, a TNF-alpha blocking agent, was instituted. An immediate response of Crohn's disease was observed and, over the next 5 weeks, the ulcer on her right ankle also healed completely.     

Hidradenitis suppurativa responding to treatment with infliximab

A series of four cases of severe recalcitrant hidradenitis suppurativa treated with infliximab is presented. All patients had failed to respond to prior medical and surgical management. Baseline Quantiferon‐TB Gold and chest radiograph were carried out before commencement of treatment. No patients had associated Crohn's disease. All patients received induction infusions of infliximab 5 mg/kg at weeks 0, 2 and 6, followed by eight weekly maintenance infusions. The total number of infusions varied between 4 and 6. Skin photography with Sartorius scoring was used to evaluate response to treatment. All patients experienced marked improvement in their disease activity, with a mean 48% improvement in Sartorius score after one infusion (week 2, P < 0.01), and 70% improvement after three infusions (week 14, P < 0.01). Time to relapse following cessation of therapy ranged from 6 weeks to 4 months. Further studies examining the efficacy of infliximab and its effect on the course of the disease, particularly relating to long‐term management, are required.     

A case of cytomegalovirus colitis following immunosuppressive treatment for pyoderma gangrenosum

We report a case of pyoderma gangrenosum (PG) complicated by cytomegalovirus (CMV)-induced colitis. A 79-year-old woman with PG was treated with corticosteroid and cyclosporin. She had blood in her stool and advancing anemia during the treatment. A colonoscopic biopsy specimen from the colon revealed typical CMV-infected cells with CMV inclusions confirmed by immunohistochemistry. Furthermore, there were many CMV-antigen-positive leukocytes, suggesting an active CMV infection, which is serious in compromised hosts. Although ulcerative colitis and Crohn's disease are well known as complications of PG, CMV enterocolitis should be considered in the differential diagnosis of enterocolitis in immunocompromised patients.     

De novo tuberculosis during infliximab therapy in a patient with Behçet disease

A woman with oculocutaneous Behçet disease developed primary tuberculosis while being treated with infliximab. A latent tuberculosis infection had been excluded before therapy. After more than 80 weeks of treatment, the patient complained of fevers, night sweats, shivering and vigorous cough. The chest x‐ray showed miliary shadowing. Mycobacterium tuberculosis was identified. The history revealed recent contact to an individual with smear‐positive tuberculosis. This constellation speaks in favor of a de novo tuberculosis infection with a fulminant course.     

Efficacy of infliximab for severe recalcitrant psoriasis after 6 weeks of treatment

Infliximab treatment has been shown to be effective for moderate-to-severe psoriasis in several large clinical trials. Nonetheless, experience with this new treatment is still needed to evaluate its efficacy and tolerance in everyday practice. In this follow-up study, we report our experience with infliximab for recalcitrant psoriasis. Nineteen patients with recalcitrant psoriasis were treated between July 2004 and December 2006 with 5 mg/kg infliximab i.v. at weeks 0, 2 and 6 followed by maintenance every 8 weeks. In three patients resistant to treatment, methotrexate was added at a 15-25 mg dose weekly after the sixth week of infliximab therapy. Pretreatment evaluations included chest X-ray, tuberculin test (5 units), full blood count, kidney and liver function tests, antinuclear antibodies and patient weight. Response to treatment, using the Psoriasis Area and Severity Index (PASI) score, and adverse effects were prospectively assessed at weeks 0, 6 and 22. At week 6, after only two infusions, 78.9% (15/19) of patients showed at least 75% improvement in baseline PASI (PASI 75). At week 22, 73.6% (14/19) patients had reached PASI 75. Three patients had a relapse. Four developed adverse effects that required suspension of infliximab therapy. No tuberculosis or lymphoproliferative disease was observed. Four patients (21%) showed apparition of positive antinuclear antibody during the course of treatment and 57.8% (11/19) of patients showed an increase in weight at week 22. Our experience shows that infliximab is a very rapidly effective treatment of severe, treatment-resistant psoriasis as soon as the sixth week of treatment.     

Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor alpha,infliximab

BACKGROUND: Psoriatic skin lesions in patients with Crohn's disease or psoriatic arthritis have shown improvement during infliximab treatment. OBJECTIVE: The purpose of our study was to systematically assess the effects of infliximab in patients with psoriatic skin lesions. METHODS: Eight patients with severe psoriasis were enrolled in an open-label clinical trial. Patients received infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6, 8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the follow-up end point. Pruritus was assessed on a scale of 0 to 3. Histologic sections were prepared from biopsy specimens of uninvolved skin and of psoriatic lesions at weeks 0, 1, and 10 to measure epidermal thickness with the use of a microscopic micrometer grid. RESULTS: The PASI diminished from 21.8 +/- 4.2 (mean +/- SE) at week 0 to 3.4 +/- 2.0 at week 10, corresponding to 10.7% +/- 4.3% of the original values (100%); on follow-up at week 14, the PASI was 7.1 +/- 2.7 (or still 33.3% +/- 11.3% of the values at week 0). Pruritus decreased from 2.5 +/- 0.26 at week 0 to 0.43 +/- 0.2 at week 10 and to 0.83 +/- 11.3 at week 14. Likewise, epidermal thickness (acanthosis) tended to normalize from 0.41 +/- 0.06 mm at week 0 to 0.14 +/- 0.02 mm at week 10. No adverse effects other than fatigue during infusion on some occasions were reported. CONCLUSION: Although psoriasis tends to recur beyond 2 months of the infusions, this open study provides evidence that infliximab is an effective treatment.     

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.     

The Role of Anti-Tumor Necrosis Factor-α Therapy in Pyoderma Gangrenosum Associated with Inflammatory Bowel Disease

Pyoderma gangrenosum (PG) is an ulcerative neutrophilic dermatosis seen in 1-5% of patients with inflammatory bowel disease (IBD). The pathogenesis of PG remains unclear, but may be related to abnormal T-cell responses and production of tumor necrosis factor (TNF)-alpha, a powerful proinflammatory cytokine. Although their use is not supported by appropriately controlled trials, corticosteroids and systemic immunosuppressants are the classical cornerstones of treatment of PG, against which they have a nonspecific effect. Successful curative or symptomatic treatment of associated disorders may lead to an improvement in PG. A new era for the management of chronic inflammatory disease began with the advent of biotherapies and particularly anti-TNFalpha therapy, which allows for a specific intervention in the immune cascade. Anti-TNFalpha therapy has improved and broadened the therapeutic options for IBD and, therefore, has brought new perspectives to management of the extra-intestinal manifestations of this disorder, including PG. To date, infliximab, etanercept, and adalimumab have been used in the treatment of PG. Published data have demonstrated that infliximab is highly effective in the treatment of PG, whether associated with IBD or not. This treatment is generally well tolerated, even as long-term therapy. However, rare and serious complications have been reported. Although infliximab is a costly drug, its use should be considered for patients with PG and particularly with corticosteroid-refractory PG associated with IBD. Additional comparative long-term studies are needed to determine the long-term efficacy and safety of anti-TNFalpha therapy and define its role in the management of PG, with or without accompanying IBD.     

Successful long-term management of refractory cutaneous and upper airway sarcoidosis with periodic infliximab infusion

A clinically refractory case of cutaneous sarcoidosis was successfully treated with infliximab infusion therapy at a dose of 5mg/kg. Skin lesions cleared dramatically and remain resolved during a 3(1/2) year follow-up, the longest follow-up reported to date. Ongoing biological drug therapy has been administered at a frequency of every 8-10 weeks. Despite cost and safety concerns, infliximab should be considered in cases of cutaneous sarcoidosis refractory to standard treatment protocols.     

Giant cells in pyoderma gangrenosum

It has been claimed that pyoderma gangrenosum (PG) lesions may contain granulomatous foci when associated with Crohn's disease. To test this assertion, we obtained clinical histories and archived cutaneous biopsies from 34 PG patients. Thirteen of these patients had inflammatory bowel disease (IBD). Immunostaining with PGM1, a macrophage marker, revealed well-formed giant cells with three or more nuclei in biopsies from 6 of 13 patients with IBD. Five of the 6 biopsies came from patients with Crohn's disease and one from a patient with ulcerative colitis. Two were peristomal. In the 21 patients who had PG without IBD, no giant cells were seen. Thus, PGM1+ histiocytic giant cells within a PG lesion may be indicative of associated IBD (p = 0.006), particularly Crohn's disease.     

A case of refractory pyoderma gangrenosum treated with a combination of Apligraf and systemic immunosuppressive agents

Pyoderma gangrenosum (PG) is a rare inflammatory ulcerative skin disease. A case of refractory PG treated with a combination of immunosuppression and Apligraf (Organogenesis, Canton, Massachusetts) is presented. Under infliximab, systemic corticosteroids, and Apligraf, the wound showed a slow but complete healing. The authors demonstrated the potential benefits of Apligraf in the healing of PG.     

Long term oral acyclovir in disseminated mucocutaneous herpes simplex: a case report.

A 24 year old woman with Crohn's disease presented initially with a severe primary genital herpes infection. After the first attack frequent recurrences occurred on the hands, feet, and genitalia. The patient was treated with oral acyclovir for 12 weeks, during which time she had two brief minor recurrences. After treatment was stopped lesions recurred at the same sites.     

Long term oral acyclovir in disseminated mucocutaneous herpes simplex: a case report

A 24 year old woman with Crohn's disease presented initially with a severe primary genital herpes infection. After the first attack frequent recurrences occurred on the hands, feet, and genitalia. The patient was treated with oral acyclovir for 12 weeks, during which time she had two brief minor recurrences. After treatment was stopped lesions recurred at the same sites.     

Refractory pyoderma gangrenosum associated with ulcerative colitis successfully treated with infliximab

Pyoderma gangrenosum (PG) is a rare, immune-mediated ulcerating skin disease. In up to 50 percent of the cases, PG is associated with underlying systemic disorders, most commonly inflammatory bowel diseases, connective tissue diseases, or hematological disorders. Herein, we present a case of refractory PG associated with ulcerative colitis (UC), successfully treated with infliximab.     

Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor α, infliximab

Background: Psoriatic skin lesions in patients with Crohn's disease or psoriatic arthritis have shown improvement during infliximab treatment. Objective: The purpose of our study was to systematically assess the effects of infliximab in patients with psoriatic skin lesions. Methods: Eight patients with severe psoriasis were enrolled in an open-label clinical trial. Patients received infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6, 8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the follow-up end point. Pruritus was assessed on a scale of 0 to 3. Histologic sections were prepared from biopsy specimens of uninvolved skin and of psoriatic lesions at weeks 0, 1, and 10 to measure epidermal thickness with the use of a microscopic micrometer grid. Results: The PASI diminished from 21.8 ± 4.2 (mean ± SE) at week 0 to 3.4 ± 2.0 at week 10, corresponding to 10.7% ± 4.3% of the original values (100%); on follow-up at week 14, the PASI was 7.1 ± 2.7 (or still 33.3% ± 11.3% of the values at week 0). Pruritus decreased from 2.5 ± 0.26 at week 0 to 0.43 ± 0.2 at week 10 and to 0.83 ± 11.3 at week 14. Likewise, epidermal thickness (acanthosis) tended to normalize from 0.41 ± 0.06 mm at week 0 to 0.14 ± 0.02 mm at week 10. No adverse effects other than fatigue during infusion on some occasions were reported. Conclusion: Although psoriasis tends to recur beyond 2 months of the infusions, this open study provides evidence that infliximab is an effective treatment. (J Am Acad Dermatol 2002;46:886-91.)     

Psoriasiform and pustular eruption induced by infliximab

Although antitumor necrosis factor (anti-TNF)-alpha therapy provides beneficial effects on various chronic inflammatory skin diseases including psoriasis, cutaneous side-effects have also been reported. We describe four patients who showed psoriasiform eruption following anti-TNF-alpha therapy (infliximab) for Crohn's disease. In all patients, Crohn's disease had responded well to infliximab. Three patients developed plaque-type psoriasiform eruption on the trunk and four extremities, while one patient showed pustular eruption on the palms and soles accompanied with plaque-type psoriasis. In all these patients, skin lesions subsided with topical application of corticosteroid ointment or psoralen plus ultraviolet A treatment.