Pyoderma Gangrenosum and Interleukin Inhibitors: A Semi-Systematic Review.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerating skin disease associated with multiple comorbidities and increased mortality. In recent decades, newer biologics such as interleukin inhibitors have been used to treat PG; however, the literature is scarce, consisting predominantly of case reports and caseseries. The aim of our review was to evaluate the effectiveness and safety of interleukin inhibitors for the treatment of PG in adults. SUMMARY: A literature search was conducted using search terms related to PG and interleukin inhibitors in databases such as PubMed, Embase, Scopus, Web of Science, and Cochrane Library. The study eligibility criteria included patients diagnosed with PG, over the age of 18, and treated with an interleukin inhibitor. Our study included 60 papers describing 81 patients fulfilling the eligibility criteria. The treatment with interleukin inhibitors resulted in 70% (95% CI 59-80%) response and 57% (95% CI 45-68%) complete response rates, and few (4%) mild adverse events, hence supporting the off-label use for the treatment of recalcitrant PG in adults. The response and complete response rates were 59% (17/29) and 38% (11/29) for anakinra, 64% (7/11) and 55% (6/11) for canakinumab, and 79% (27/34) and 71% (24/34) for ustekinumab, respectively. Limitations include publication bias that might have overestimated the efficacy as successful cases responding to treatment are more likely to be reported than nonresponding cases. Additionally, the heterogeneity of the treatment groups does not allow conclusions of superiority or inferiority of the different interleukin inhibitors to be drawn. Further studies are needed to investigate the efficacy of the different interleukin inhibitors and to investigate the importance of underlying disease for treatment response.

[Pyoderma gangrenosum].

Pyoderma gangrenosum is a diagnostic and therapeutic challenge. A misdiagnosis or delayed diagnosis can lead to increased morbidity and death. A fast workup and initiation of treatment is essential. In this review, we present new diagnostic criteria, which can ease the diagnosis, and we summarise the evidence of different treatment modalities. The evidence points towards local immunosuppressive treatment in mild disease, supplemented by systemic glucorticosteroids, ciclosporin or tumour necrosis factor-alpha inhibitors in severe cases. Other biologics are emerging.

Pyoderma Gangrenosum: A Retrospective Study of Clinical Charac-teristics, Comorbidities, Response to Treatment and Mortality Related to Prednisone Dose.

Pyoderma gangrenosum is an uncommon ulcerative neutrophilic dermatosis. Clinical presentation, location and associated diseases are diverse. Treatment of pyoderma gangrenosum includes treating the underlying comorbidity supplemented with topical and/or systemic agents. However, treatment is often challenging. The aim of this study was to explore the diversity of pyoderma gangrenosum and its treatments. A total of 64 patients with pyoderma, at the Department of Dermatology, Aarhus University hospital, Denmark, were included in the study. The patients' records were reviewed over a 6-year period for clinical presentation, associated diseases, treatments and response to treatment, time to mortality after diagnosis and prednisone dose over time. A variety of accompanying comorbidities were found, including a possible association with diabetes. Tumour necrosis α inhibitors were used as third- or fourth-line therapy, but showed the shortest time to remission, and use of prednisone was associated with a higher mortality rate. These findings are discussed in relation to future approaches to treatment of pyoderma gangrenosum.

Pyoderma gangrenosum and tumour necrosis factor alpha inhibitors: A semi-systematic review.

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease that presents a therapeutic challenge. Tumour necrosis factor alpha (TNFα) inhibitors have been reported to successfully control PG. Our aim was to systematically evaluate and compare the clinical effectiveness of TNFα inhibitors in adults with PG. A literature search including databases such as PubMed, Embase, Scopus, and Web of Science was conducted, using search terms related to PG and TNFα inhibitors. Studies and case reports were included if patients were diagnosed with PG, over the age of 18 and administered TNFα inhibitor. A total of 3212 unique citations were identified resulting in 222 articles describing 356 patients being included in our study. The study we report found an 87% (95% CI: 83%-90%) response rate and a 67% (95% CI: 62%-72%) complete response rate to TNFα inhibitors. No statistically significant differences in the response rates (P = 0.6159) or complete response rates (P = 0.0773) to infliximab, adalimumab, and etanercept were found. In our study TNFα inhibitors demonstrated significant effectiveness with response and complete response rates supporting the use of TNFα inhibitors to treat PG in adults. Our study suggests that there is no significant difference in effectiveness among infliximab, adalimumab, and etanercept.

Accelerated wound healing with combined NPWT and IPC: a case series.

Negative pressure wound therapy (NPWT) and intermittent pneumatic compression (IPC) have traditionally been used in patients with chronic complicated non-healing wounds. The aim of this study (retrospective case series) was to describe the use of NPWT in combination with IPC in patients with a relatively short history (2-6 months) of ulcers. All wounds showed improved healing during the treatment period with marked or moderate reduction in ulcer size, and granulation tissue formation was markedly stimulated. Oedema was markedly reduced due to IPC. Treatment was generally well tolerated. The results of this study indicate that combined NPWT and IPC can accelerate wound healing and reduce oedema, thus shortening the treatment period. Therefore, patients may have a shorter healing period and may avoid entering a chronic wound phase. However, controlled studies of longer duration are needed in order to show the long-term effect of a more accelerated treatment course.

Clinical efficacy of a silver-releasing foam dressing in venous leg ulcer healing: a randomised controlled trial.

Biatain and Biatain-Ag are two identical wound dressings except the fact that Biatain-Ag releases silver. In the present multinational double-blinded randomised controlled trial the effect of the two dressings were compared for treatment of venous leg ulcers. A total of 181 patients were treated for 6 weeks with either Biatain or Biatain-Ag followed by 4 weeks treatment with Biatain. Biatain-Ag showed superior performance in relative wound area reduction after 6 weeks treatment and the estimated treatment difference increased after 10 weeks indicating that the effect of silver continues at least for 4 weeks after treatment. A subgroup of the patients differed significantly from the others with respect to parameters associated with a poor healing prognosis; patients were older, had significant history of venous thrombosis, larger ulcers with longer duration and more often recurrent. For this subgroup of patients Biatain-Ag showed significant (P < 0·05) better performance in terms of relative ulcer area reduction and healing rate. In conclusion, this study suggests the superior performance of Biatain-Ag compared with the non silver-releasing dressing Biatain in particular for patients having ulcers associated with a poor healing prognosis.

[Cancer unmasked or provoked by immunosuppressive therapy]. / Cancer demaskeret eller fremprovokeret hos patienter i immunsuppressiv behandling

The association between immunosuppressive therapy and cancer is to discussion. The overall risk is, however, still to be fully investigated. We describe two patients who had skin manifestations treated with immunosuppressive therapy and shortly afterwards were diagnosed with cancer. The skin diseases in question, vasculitis and pyoderma gangraenosum, can themselves be associated with cancer. However, treating these diseases with immunosuppressive therapy may potentially unmask or provoke an underlying cancer.

Clinically relevant pain relief with an ibuprofen-releasing foam dressing: results from a randomized, controlled, double-blind clinical trial in exuding, painful venous leg ulcers.

The objective of this 6-week, 120-patient, double-blind, randomized, controlled trial was to investigate if a foam dressing with ibuprofen provided clinically relevant pain relief (PAR) for exuding, painful venous leg ulcers in comparison with a similar foam dressing without ibuprofen. Primary outcome parameter was PAR compared with baseline pain during the first 5 days of the investigation. PAR was registered by the patient morning and evening. Main end point was proportion of patients reporting a summed PAR score of at least 50% of the total maximum PAR (i.e., responders) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p = 0.0438). There were 34% responders in the ibuprofen foam group vs. 19% in the comparator group (NNT = 6.8). When evening data were analyzed separately to evaluate PAR over daytime, NNT was 5.3. Wound healing parameters and adverse events were comparable. In conclusion, in this study, the ibuprofen foam dressing provided clinically relevant PAR for patients with exuding, painful venous ulcers.

Thalidomide in 42 patients with prurigo nodularis Hyde.

The aim of this study was to describe the use of thalidomide in the treatment of prurigo nodularis Hyde (PNH) refractory to other treatments or in cases where other treatments cannot be used due to side effects. 77 medical records were retrospectively reviewed for the following data: sex, age, age at the beginning of thalidomide treatment, dermatological diagnosis, duration of the skin disease, previous treatments, indications for treatment with thalidomide, effect of treatment, duration of treatment with thalidomide, reasons for cessation of thalidomide treatment, and side effects. 54 patients had PNH. All patients were refractory to standard therapy or had side effects to treatment. 42 patients were treated with thalidomide and the majority of patients experienced clinical improvement. The most common reason for discontinuation of therapy was side effects, the most frequent being peripheral neuropathy and sedation. Thalidomide effectively treats PNH refractory to standard medications. However, physicians must be aware of possible side effects, especially peripheral neuropathy.

Traumatic pyoderma gangrenosum of the face: pathergy development after bike accident.

We present a patient who developed pyoderma gangrenosum (PG) twice, initially after a minor trauma and later after reconstructive surgery. This case is presented to address the frequent misdiagnosis and mistreatment of PG by surgeons. It is of great importance that PG is diagnosed and of even great importance that surgery is avoided in order to prevent pathergy. Our case adds to the understanding that the diagnosis is based on the clinical and histopathological findings and by excluding other causes of skin ulcers. When a wound is not healing despite relevant local wound management and systemic treatment if needed, the clinician should always suspect PG. Early diagnosis and treatment is crucial in the management of PG and surgery is contraindicated.

Assessment and management of persistent (chronic) and total wound pain.

Persistent (chronic) wound-related pain is a common experience that requires appropriate assessment and treatment. It is no longer adequate for health care professionals to concentrate on the acute (temporary) pain during dressing change alone. The study provides useful recommendations and statements for assessing and managing total wound-related pain for patients, health care professionals and other policymakers. The recommendations have been developed with the involvement of an interprofessional panel of health care professionals from around the world.

Managing painful chronic wounds: the Wound Pain Management Model.

Chronic wound pain is not well understood and the literature is limited. Six of 10 patients venous leg ulcer experience pain with their ulcer, and similar trends are observed for other chronic wounds. Chronic wound pain can lead to depression and the feeling of constant tiredness. Pain related to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase.

A fatal case of malignant atrophic papulosis (Degos' disease) in a man with factor V Leinden mutation and lupus anticoagulant.

Malignant atrophic papulosis (Degos' disease) is a very rare condition characterized by atrophic papular skin lesions and variable association of systemic involvement. We describe a 33-year-old man who presented with a widespread skin eruption consistent with malignant atrophic papulosis. During the course of the disease he even developed penile ulcerations, a symptom that has been reported only a few times previously. He subsequently died of multiple perforations of the small bowel 2.5 years after onset of the disease. Laboratory investigations revealed a mutation of factor V Leiden and the presence of lupus anticoagulant, but no anti-cardiolipin antibodies. The patient was treated with narrow-band ultraviolet (UV)B, prednisolone and, later, aspirin, pentoxifyllin and warfarin. Despite this very intensive anticoagulant and anti-platelet therapy, the treatment had no effect on the skin lesions and could not prevent systemic involvement.

New vitamin D analogs in psoriasis.

Psoriasis is a common inflammatory and hyperproleferative skin disease characterized by infiltrated plaques of the skin and may involve nails, scalp and intertreginous areas. Recent years of research has shown that psoriasis can be treated topically with analogs of vitamin-D(3). Impaired differentiation and increased proliferation of epidermal keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated that analogs of vitamin D(3) increase differentiation and inhibit proliferation of keratinocytes. Topical treatment with analogs of vitamin D(3) have in a number of trials shown improvement of psoriasis. Vitamin D analogs show the same efficacy as potent topical corticosteroids and do not produce skin atrophy during long-term therapy. Vitamin D analogs can be used both as monotherapy and in combination with topical corticosteroids, UVB, PUVA, acitretin, methotrexate and cyclosporine. The vitamin D(3) analog calcipotriol has been investigated in most detail and is available as an ointment, a cream and as a scalp solution. From clinical studies involving several thousands of patients, it can be concluded that calcipotriol is efficacious, safe and well-tolerated even on a long term basis.