Severe skin ulcer caused by taking lenvatinib after proton beam therapy.

A 69-year-old man was treated with lenvatinib after three sessions of proton beam therapy (PBT) for hepatocellular carcinoma. Five months after administration of lenvatinib, a dermatitis with huge skin ulcer formed in the site of PBT irradiation. Lenvatinib was immediately withdrawn, but the skin ulcer continued growing until about 2 weeks later. With topical and antibiotic treatment, the skin ulcer resolved after about 4 months. After administration of lenvatinib, potential skin damage due to PBT at the irradiated site may have become apparent. This is the first report describing skin ulcer by the combination of lenvatinib administration and PBT.

Bizarre Cutaneous Ulcers due to Self-Administered Intravenous Dexketoprofen Trometamol.

Systemic non-steroidal anti-inflammatory drug use may result in various cutaneous complications including maculopapular rash, fixed drug eruption, urticaria, and angioedema most frequently. However extensive cutaneous ulcers in relation to intravenous dexketoprofen trometamol use has not been identified before although cutaneous ulcers have been described in association with several opioids. Herein, we would like to present a 27-year-old male with a 1-year history of progressive deep cutaneous ulcers due to long term abusive intravenous use of dexketoprofen trometamol.

Skin ulcers as a complication of short-term use of phenazopyridine in an old man: A case report.

INTRODUCTION: Phenazopyridine is an azo dye, which exerts local anesthetic or analgesic action on urinary tract mucosa through an unknown mechanism. Besides its common complications including orange discoloration of the urine and gastrointestinal problems, it may have rare side effects like hemolytic anaemia, methemoglobinemia, renal failure, and skin changes. We reported a paraplegic man with skin ulcers on scretom and right foot after about 3 days of phenazopyridine use CASE REPORT: A 62-year-old man presented with flesh shaped deep ulcers in lower parts of the body. He declared that at first a bluish discoloration was developed in the lower extremities and scrotum skin after use of eight phenazopyridine tablets (200 mg) and then these lesions turned to blisters and ulcers and they were prurient. The patient underwent sonography and CT-angiography; however, no pathologic findings were found. He just received losartan for many years as past drug history. According to the history, a delayed drug hypersensitivity reaction was suspected and the patient wounds healed after using special type of dressings and antibiotic therapy regarding positive wound cultures. CONCLUSION: Phenazopyridine severe skin changes are hardly reported. We described a case who experienced severe skin reactions and ulcers following phenazopyridine use not related to other complications including renal dysfunction, methemoglobinemia, and hemolytic anemia.

Methotrexate Cutaneous Ulceration: A Systematic Review of Cases.

BACKGROUND: Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series. OBJECTIVE: To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration. METHODS: A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases. RESULTS: 114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality. LIMITATIONS: Selection bias present due to abstraction from case reports and case series. CONCLUSION: Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.

Association between subcutaneous steroid injection for extravasation of vesicant anticancer drugs and skin ulcers requiring surgery.

PURPOSE: Although subcutaneous steroid injections are conventionally used to treat extravasation of vesicant anticancer drugs, their effects on the extravasation site remain unclear. We investigated the association between subcutaneous steroid injection in patients with extravasation of vesicant anticancer drugs and incidence of skin ulcers requiring surgery. METHODS: We performed a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database. We identified patients with extravasation of vesicant anticancer drugs who were prescribed steroid ointment or cream on the same day as vesicant drug use between July 2010 and March 2019. The exposure group consisted of patients who had received subcutaneous steroid injections and local anesthetic in addition to topical steroids, whereas the control group had received topical steroids alone. The outcome was the incidence of skin surgical procedures during hospitalization. We performed a mixed-effect logistic regression analysis with random intercept for each hospital to compare outcomes between the groups. RESULTS: We identified 7284 patients from 704 hospitals, including 3713 patients who had received topical steroids alone and 3571 who had received subcutaneous steroid injection in addition to topical steroids. According to mixed-effect logistic regression analysis, subcutaneous steroid injection was significantly associated with a higher incidence of skin surgery (odds ratio, 1.61; 95% confidence interval, 1.14-2.26; P = 0.007). Barthel Index, type of cancer, and type of vesicant drugs were also associated with surgery. CONCLUSIONS: Subcutaneous steroid injections after extravasation of vesicant anticancer drugs are associated with more frequent skin surgery. Randomized controlled trials are required to evaluate the safety and effectiveness of steroid injection.

Skin ulcers caused by ruxolitinib in a patient with chronic cutaneous graft-versus-host disease.

INTRODUCTION: Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT). In the treatment of chronic GVHD, skin directed therapy, systemic corticosteroids, calcineurin inhibitors (such as cyclosporine (CsA) and tacrolimus), rituximab, mycophenolate mofetil (MMF), extracorporeal photopheresis (ECP) and ruxolitinib are used. CASE REPORT: We present an 18 year old male with Philadelphia chromosome positive acute B lymphoblastic leukemia, treated with allogeneic HCT from a full matched sibling donor. The patient had grade 2 chronic cutaneous GVHD resistant to corticosteroids, CsA, MMF, and ECP treatment. Three months after initiation of ruxolitinib therapy, the patient developed skin ulcers on his lower extremities. MANAGEMENT & OUTCOME: The biopsy revealed that the changes were caused by the drug reactions. We suspected ruxolitinib as the likely cause of these ulcerative lesions after evaluating the adverse drug reaction probability scale. The adverse drug score was 4, therefore, ruxolitinib treatment was discontinued. Ulcerative lesions fully recovered after 4 weeks of follow-up. DISCUSSION: Ruxolitinib is used in the treatment of chronic GVHD that has been resistant to steroids and other salvage therapies. In our case, ruxolitinib was used as a salvage therapy in a patient who had refractory chronic skin GVHD. Ruxolitinib-related skin lesions with ulcers of lower extremities and whole body erythematous skin lesions were reported previously in patients with myelofibrosis. The pathophysiology of ruxolitinib related skin ulcers is unknown. Skin changes of patients using ruxolitinib should be closely monitored, and newly developing lesions should be suspected of being drug-related and biopsied.

Methotrexate-Induced Cutaneous Ulcers: A Rare Side Effect.

Methotrexate is often prescribed for the treatment of autoimmune conditions. There are many well-known side effects of methotrexate, a lesser known side effect is methotrexate-induced cutaneous ulceration. Only eight cases have been reported in the literature. Here we report a ninth case report of methotrexate-induced cutaneous ulceration in a 73-year-old female who had recently had her methotrexate dose increased for her seronegative rheumatoid arthritis. She presented to the emergency department with painful ulcerative nodules on her hands. In addition, laboratory evaluation found her to be pancytopenic. Methotrexate was discontinued and patient was given a dose of leucovorin. Within a couple weeks of methotrexate discontinuation, the ulcers resolved. Our case in addition to a review of the literature suggests that methotrexate-induced cutaneous ulceration may be an indication of life-threatening pancytopenia.

Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds.

The short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.