Chronic ulcer in a patient with essential thrombocythemia taking hydroxyurea.

Chronic skin ulcers in patients with suspected pyoderma gangrenosum can, on closer inspection and further workup, have a different cause. Recognition of key features on clinical examination such as the presence of atrophie blanche is key to avoid misdiagnosis of pyoderma gangrenosum and its subsequent treatment with high-dose corticosteroids and other immunosuppressive medications.

Tyrosine kinase inhibitors-associated pyoderma gangrenosum, a systematic review of published case reports.

Pyoderma gangrenosum is a rare ulcerative dermatosis. It may be caused by some drugs, including small molecule tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the reported evidence of pyoderma gangrenosum associated with the use of these drugs. A systematic electronic literature search of PubMed and Embase was conducted. In these databases, search terms describing pyoderma gangrenosum were combined with TKIs. Fifteen case reports (eight cases associated with sunitinib, two with imatinib, two with ibrutinib, one with gefitinib, one with pazopanib, and one with dabrafenib and trametinib) were identified over the 14 years. The average Naranjo score of these cases is 6.6, which indicates a probable adverse drug reaction. Pyoderma gangrenosum is a probable and reversible drug reaction associated with some TKIs. Detailed medical history can help to prompt diagnosis of drug-induced pyoderma gangrenosum. Clinicians should be aware of TKI-associated pyoderma gangrenosum when caring for the skin of oncologic patients undergoing therapy with kinase inhibitors.

Onset of Pyoderma Gangrenosum in Patients on Biologic Therapies: A Systematic Review.

OBJECTIVE: To summarize clinical outcomes of paradoxical pyoderma gangrenosum (PG) onset in patients on biologic therapy. METHODS: The authors conducted MEDLINE and EMBASE searches using PRISMA guidelines to include 57 patients (23 reports). RESULTS: Of the included patients, 71.9% (n = 41/57) noted PG onset after initiating rituximab, 21.1% (n = 12/57) noted tumor necrosis factor α (TNF-α) inhibitors, 5.3% (n = 3/57) reported interleukin 17A inhibitors, and 1.8% (n = 1/57) reported cytotoxic T-lymphocyte-associated protein 4 antibodies. The majority of patients (94.3%) discontinued biologic use. The most common medications used to resolve rituximab-associated PG were intravenous immunoglobulins, oral corticosteroids, and antibiotics, with an average resolution time of 3.3 months. Complete resolution of PG in TNF-α-associated cases occurred within an average of 2.2 months after switching to another TNF-α inhibitor (n = 1), an interleukin 12/23 inhibitor (n = 2), or treatment with systemic corticosteroids and cyclosporine (n = 3), systemic corticosteroids alone (n = 1), or cyclosporine alone (n = 1). CONCLUSIONS: Further investigations are warranted to determine whether PG onset is associated with underlying comorbidities, the use of biologic agents, or a synergistic effect. Nevertheless, PG may develop in patients on rituximab or TNF-α inhibitors, suggesting the need to monitor and treat such adverse effects.

Pyoderma gangrenosum associated with levamisole-adulterated cocaine in a c-ANCA positive patient.

Pyoderma gangrenosum (PG) is an inflammatory, ulcerative condition that is characterized by painful ulcers that commonly present on the lower extremities. Up to half of PG cases are associated with underlying systemic disease, including inflammatory bowel disease, various autoimmune conditions, and malignancy. Another well-known association is the manifestation of PG with recreational cocaine use, especially cocaine contaminated with the adulterant agent levamisole. Once utilized for its immunomodulatory capabilities, levamisole was withdrawn from the market in 2002. It has since been repurposed to potentiate the amphetamine-like effects and duration of cocaine and has reduced preparation cost. We present a 52-year-old woman with chronic maxillary sinusitis and cocaine use disorder presenting with a two-week history of painful ulcers on bilateral lower extremities, each with a purulent base and undermined, violaceous borders. Urine toxicology was positive for cocaine and serologic studies were positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and lupus anticoagulant. Underlying conditions, especially that of granulomatosis with polyangiitis, were considered and ultimately ruled out. The patient's lesions exhibited a marked response with a short course of oral corticosteroids, typical of PG associated with levamisole. This case highlights the crucial role that drug abstinence plays in the prevention of recurrence.

Pembrolizumab-associated pyoderma gangrenosum in a patient with metastatic squamous cell carcinoma.

Pyoderma gangrenosum (PG) is a rare, ulcerative neutrophilic dermatosis that has been reported in association with certain medications. Recognition of medications that trigger PG may help to better understand the pathogenesis of the condition and to provide earlier diagnosis and treatment for affected patients. Herein, we report a case of new-onset PG following initiation of the checkpoint inhibitor pembrolizumab for the treatment of metastatic cutaneous squamous cell carcinoma. Our case was resistant to intralesional corticosteroid therapy, but ultimately improved with systemic corticosteroids and cessation of pembrolizumab.

Pyoderma gangrenosum-like lesions provocated by botulinum injections.

Botulinum toxin (BoNT) is a valuable therapeutic tool with several medical indications and the most popular of all cosmetic procedures worldwide. This is the reason for the growing number of unregistered products that may be the reason for adverse reactions. We present a case of a 51-year-old woman, who developed a pyoderma gangrenosum-like reaction at injection sites after the administration of an unregistered BoNT product by a beautician. The clinical course, the morphology of the lesions, the result of histopathological biopsy, and the response to the treatment meets the criteria for diagnosis of pyoderma gangrenosum. The case presented by us is the first adverse reaction of this type after BoNT administration.

Pyoderma gangrenosum adverse event with Rituximab use: A postmarketing pharmacovigilance analysis.

Rituximab is a monoclonal antibody that is used for the treatment of certain malignancies and autoimmune conditions. Pyoderma gangrenosum is a rare painful ulcer that can be fatal in some cases and can also reoccur after treatment. The objective of this paper was to analyze whether a statistically significant signal exists between Rituximab and pyoderma gangrenosum in the Food and Drug Administration Adverse Event Reporting System (FAERS). A disproportionality analysis was carried out on cases from January 1, 2004 to March 31, 2019 in the FAERS. Frequentist methods of relative reporting ratio, reporting odds ratio (ROR), and proportional reporting ratio (PRR) and the Bayesian-based IC025 metric were used in order to assess the adverse event signal. Thirty-two cases were found in FAERS in which the drug Rituximab was administered and pyoderma gangrenosum was reported as an adverse event. The lower 95% CI of the information component was 0.97, the lower 95% CI of ROR was 2.18, the PRR was 3.09 and Chi-squared was 42.16, which indicates a statistically significant signal. The signal is supported by six case reports in the literature that describe a total of 14 patients who developed pyoderma gangrenosum after Rituximab administration. When administering Rituximab, clinicians should monitor for the occurrence of symptoms representing pyoderma gangrenosum.

Tolerability and safety of long-term rituximab treatment in systemic inflammatory and autoimmune diseases.

Rituximab, an anti-CD20 monoclonal antibody causing selective B-cell depletion, is used for various systemic inflammatory and autoimmune diseases (SIADs). Long-term safety data on rituximab are limited. The objectives of this study were to evaluate the long-term safety and tolerability of rituximab treatment for SIADs. A retrospective, single-center observational study including all patients ≥ 16 years treated with rituximab for SIADs was performed. The electronic medical records were reviewed, and data concerning indication and duration of rituximab treatment, prior and concurrent immunosuppressive therapy, and adverse events such as infections requiring hospitalization, dysgammaglobulinemia and end organ damage, were collected. A total of 70 patients were included, with a median treatment duration of 54 months, ranging 30-138 months. The most common indications for rituximab treatment were granulomatosis with polyangiitis (22.9%), primary Sjögren's syndrome (20.0%) and systemic lupus erythematosus (14.3%). Infections and persistent dysgammaglobulinemia were the most common adverse events, occurring in 34.3% and 25.7%, respectively. A total of 64 infections were observed in 24 (34.3%) patients, including 1 case of fatal infection. Seventeen patients performed B-cell quantitation during the first 2 years following discontinuation, of which only four (19.0%) demonstrated B-cell reconstitution. End organ damage occurred in two patients, presenting as pyoderma gangrenosum and interstitial pneumonitis. No opportunistic infections were observed. Three patients died during the observational period, of which one was due to lethal infection. This study presents observational data with long treatment duration. It demonstrates that long-term rituximab treatment is relatively well tolerated, and that no cumulative side effects were observed.

Pyoderma Gangrenosum Associated with Sunitinib: A Case Report.

Pyoderma gangrenosum (PG) is an inflammatory neutrophilic dermatosis that presents with painful, sterile ulcers. Drug-induced PG is a rare condition; propylthiouracil, granulocyte colony-stimulating factor, and sunitinib are drugs that have been implicated to date. This article presents a case of PG associated with sunitinib.

A case of pyoderma gangrenosum induced by insulin.

Pyoderma gangrenosum (PG) is a rare auto-inflammatory, neutrophilic, ulcerative disorder characterised by acutely painful, rapidly spreading, sterile ulcers over the trunk and lower limbs. The pathogenic mechansim of PG is under constant evolution and drugs are emerging to be a an important trigger. In the literature, 52 cases of drug-induced PG have been documented, of which cocaine laced with levamisole has shown most direct association, with a mean Naranjo score of 9. Other drugs probably associated with PG are isotretinoin, sunitinib, and propylthiouracil. We describe a case of a 59-year-old male who had multiple well-defined ulcers with a violaceous, undermined edge limited to the site of subcutaneous injection of insulin. Histopathological examination showed psoriasiform hyperplasia in the epidermis, with abundant infiltration of neutrophils in the dermis, consistent with the clinical diagnosis of PG. As per the modified Naranjo algorithm, the patient's total score was 7, indicating insulin to be the probable causative agent in our case. So, compiling temporal localisation of lesions to the site of administration of insulin and clinical, histopathological, and Naranjo score evidence all prompt the diagnosis of PG. Insulin stimulates the release of matrix-metalloproteinases 9 which acts as endopeptidases and also results in the chemotaxis of neutrophils, causing ulcer formation. This is the first case reporting PG triggered by insulin.

Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare autoinflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the aetiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum. In total, we found 43 cases of drug-induced PG. Most of them were caused by colony-stimulating factors and small-molecule tyrosine kinase inhibitors. We propose that drugs induce PG through various mechanisms such as dysfunctional neutrophil migration and function, dysregulated inflammatory response, promotion of keratinocyte apoptosis and alteration of epigenetic mechanisms. PG is a rare condition with complex pathophysiology and drug-induced cases are even more scarce; this is the main limitation of this review. Understanding the possible mechanisms of drug-induced PG, via abnormal neutrophil migration and function, abnormal inflammation, keratinocyte apoptosis and alteration of epigenetic mechanisms would help to better understand the pathogenesis of PG and ultimately to optimize targeted therapy.

[Pyoderma gangrenosum associated with anti-proteinase 3 antineutrophil cytoplasmic antibodies (PR3-ANCA) induced by propylthiouracil]. / Pyoderma gangrenosum avec anticorps anti-cytoplasme des neutrophiles de type anti-protéinase 3 (PR3-ANCA) induits par le propylthiouracile.

BACKGROUND: Synthetic antithyroid drugs are often used in the treatment of hyperthyroidism, regardless of aetiology. They may cause various side effects, including the development of anti-neutrophil cytoplasmic antibodies (ANCA), ANCA-associated vasculitis, and neutrophilic dermatoses. Propylthiouracil (PTU) is the antithyroid drug most frequently implicated in ANCA-associated diseases specifically involving anti-myeloperoxidase ANCA (MPO-ANCA). To our knowledge, there are no clinical reports describing the association of pyoderma gangrenosum (PG) and anti-proteinase3-ANCA (PR3-ANCA) induced by PTU, with ANCA levels decreasing after antithyroid drug withdrawal. PATIENTS AND METHODS: A 68-year-old woman was treated with propylthiouracil (PTU) for toxic multinodular goitre. She presented necrotic ulceration of the lower abdomen. The patient's history, physical examination, and bacteriological and histological samples led to a diagnosis of pyoderma gangrenosum. This pyoderma involved ANCA with antigenic specificity for proteinase 3. Withdrawal of PTU and a short course of corticosteroids and cyclosporine resulted in rapid and complete resolution of the pyoderma gangrenosum as well as a decrease in ANCA. No relapse was observed one year after cessation of treatment. DISCUSSION: We report a case of PG associated with PR3-ANCA induced by PTU, without any demonstrable vasculitis.