[Hydroxychloroquine-not always a harmless drug for off label use in dermatology]. / Hydroxychloroquin ­ nicht immer ein harmloses Medikament für den Off-label-Gebrauch in der Dermatologie.

Hydroxychloroquine is used for treatment of inflammatory diseases. It is considered to have few adverse effects. We report on a woman who developed a severe skin rash after intake of hydroxychloroquine, which she received for treatment of her lichen planopilaris. Based on the clinical, laboratory and histological findings the diagnosis of a drug reaction with eosinophilia and systemic symptoms (DRESS)-like drug reaction was established. Our case illustrates that hydroxychloroquine can lead to severe adverse effects in rare cases and that patients receiving this drug must be thoroughly informed.

Immune checkpoint inhibitor-induced lichenoid drug eruption-sparing scar burns.

The authors present a striking case of a patient experiencing a lichenoid drug eruption secondary to immunotherapy, curiously sparing scarred skin from past burns. We observed vastly higher amounts of inflammatory lymphoid cells staining for PD-1; 70% in skin with a lichenoid drug reaction and 50% in scarred skin. The lack of a lichenoid reaction at sites of scarred skin may indicate that a basement membrane component may be causative for a lichenoid drug eruption.

Drug Eruption From Atorvastatin: With Initial Misdiagnosis of Tinea Cruris.

Objective To present the case of a Latin man 68 years of age who presented to the emergency department with a rash to the right side of his groin 10 weeks after switching from simvastatin 40 mg daily to atorvastatin 40 mg daily. Background Prior to switching to atorvastatin, the patient had been taking simvastatin for 21 years without rash. The rash progressed bilaterally to his arms and hands, legs, buttocks, back, and trunk before the patient was seen by dermatology and atorvastatin was discontinued. Results Within six weeks of discontinuation of atorvastatin, the rash resolved with remaining pigmentation changes. The adverse effect was documented in the patient's chart, and dermatology recommended avoiding other statins in the future. Settings Ambulatory clinic pharmacy practice, emergency room, or urgent care centers. Practice Considerations Atorvastatin is a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor or statin that has been FDA approved for the prevention of atherosclerotic cardiovascular disease (ASCVD) and treatment of hypercholesterolemia since 1996. Despite widespread use of atorvastatin over many years, only a handful of published cases report drug eruption from its use. Previous case reports have found that retrial of statins may cause similar drug eruption. Conclusion Pharmacists should consider HMG-CoA reductase inhibitors as a possible cause of new onset rash and should not retrial an alternative statin.

Cetuximab severe cutaneous toxicity a gateway for bacteremia: case report.

EGFR inhibitors used in the treatment of metastatic wild-RAS colorectal cancer in combination with chemotherapy are associated with dermatologic side events that are low grade in most cases. We report a case of severe cutaneous toxicity secondary to cetuximab associated with bacterial cellulitis. A 57-year-old woman with metastatic adenocarcinoma of the colon, receiving FOLFIRI and Cetuximab as a first-line treatment, presented with a severe erythematous rash and xerosis resistant to local treatment with moisturizing emollients. Few days later, the patient becomes febrile, and the rash becomes more diffuse with a sandpaper appearance on the face, neck, chest, and flexor creases with exfoliation of large areas of skin. A bacterial cellulitis secondary to a dermatologic severe toxicity of Cetuximab was suspected. The patient started on antibiotics and local treatment with good response. This is a life-threatening cutaneous toxicity of cetuximab with secondary bacterial infection. Early recognition of cutaneous side effects of EGFR inhibitors is important to prevent such type of toxicities.

Cutaneous eruptions from ibrutinib resembling epidermal growth factor receptor inhibitor-induced dermatologic adverse events.

BACKGROUND: Ibrutinib is an oral inhibitor of Bruton tyrosine kinase that is approved by the United States Food and Drug Administration for several lymphoproliferative disorders and chronic graft-versus-host disease. OBJECTIVE: To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor (EGFR) inhibitor-induced dermatologic adverse events. METHODS: Single-center retrospective cohort of patients referred to the Skin Toxicities Program for treatment of cutaneous eruptions while taking ibrutinib. RESULTS: Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae, or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. Most patients were able to continue ibrutinib therapy with focused treatment of their cutaneous toxicities. LIMITATIONS: This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. CONCLUSIONS: With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Fidaxomicin-Associated Hypersensitivity Reactions: Report of a Morbilliform Drug Eruption.

PurposeWe report a probable case of morbilliform drug eruption secondary to fidaxomicin in a patient with Clostridioides difficile infection (CDI). Summary: A 62-year-old female presented to our institution's emergency department (ED) with symptoms consistent with Clostridioides difficile infection. The patient was prescribed 2 weeks of oral vancomycin for CDI prior to presentation. Given insufficient response to vancomycin, the patient was started on fidaxomicin with a planned 10-day course. After 2 doses of fidaxomicin, the patient developed a rash on her back that spread within 24 hours. The patient did not experience relief upon administration of a variety of medications for allergic reaction. Improvement was noted upon discontinuation of fidaxomicin. The Food and Drug Administration reports that < 2% of adults treated with fidaxomicin experience a rash as an adverse effect. Conclusion: Fidaxomicin was a probable cause of morbilliform drug eruption in our patient with CDI. The patient improved upon discontinuation of fidaxomicin.

Tuberculosis treatment-related lichenoid drug eruptions.

Tuberculosis is one of the leading causes of death from infectious diseases in adults worldwide. Drug hypersensitivity in tuberculosis is an important problem affecting the treatment process. Although treatment is started with isoniazid, rifampicin, ethambutol, and pyrazinamide in drug-sensitive tuberculosis patients, it may not always be continued in this way. When hypersensitivity develops under antituberculosis treatment, type 4 hypersensitivity is the most common, and maculopapular drug eruption develops as a subgroup. Lichenoid drug eruption is very rare. We present our case who was diagnosed with pulmonary tuberculosis, who developed lichenoid drug eruption while receiving treatment, and whose treatment was completed by giving the new regimen with successful desensitization.

Fixed drug eruptions - the common and novel culprits since 2000.

A fixed drug eruption (FDE) is a common cutaneous adverse drug reaction which occurs following administration of an offending drug. The aim of this review is to provide an update on the list of drugs causing FDE, with a focus on emerging drug culprits reported since the start of the century. Across published literature, triggers for FDE are widely varied. The most frequently implicated drugs include analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs] and paracetamol) and antibiotics. Co-trimoxazole is perhaps the most well described single agent. Since the start of the century there have been over 200 drugs named in case reports on FDE. Newer, novel agents of note include cyclooxygenase-2 specific inhibitors, fluconazole, and phosphodiesterase 5 inhibitors. Other implicated drugs include vaccines, such as various SARS-CoV-2 vaccines. Drugs incriminated in FDE vary based on the geographical region studied and prescribing patterns at a given time. Newer drugs continue to enter the market and are playing an increasing role in the field of FDE. Awareness of rarer culprits and emerging novel agents can help identify a trigger, allowing for prompt withdrawal of the causative agent, preventing recurrence.

Investigation of Hypersensitivity Reactions in Carboplatin Desensitization Therapy.

BACKGROUND/AIM: Carboplatin is a key drug in the treatment of ovarian cancer, but hypersensitivity reactions (HSRs) may occur with repeated use. PATIENTS AND METHODS: Thirty-seven ovarian cancer patients treated with carboplatin desensitization therapy were reviewed retrospectively. The treatment completion rate and toxicity were examined. RESULTS: The carboplatin desensitization completion rate was 86.5%. Toxicity was Grade 0, 1, 2, and 3 in 17, 5, 10, and 5 patients, respectively. Erythema was the most frequent toxicity (36.8%), most commonly affecting the arm (23.5%). Furthermore, all HSRs were classified into: skin, respiratory, digestive, circulatory, and neurological. The completion rate of desensitization was significantly lower in patients with two or more target organs affected (p<0.001). CONCLUSION: The main symptoms of HSRs, the most common sites of HSRs, and the criteria for discontinuing desensitization therapy identified in this study are useful information for the safe implementation of carboplatin desensitization therapy.

Symmetrical drug-related intertriginous and flexural exanthema/baboon syndrome induced by traditional Chinese medicine.

BACKGROUND: Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) refers to an uncommon cutaneous adverse reaction that symmetrically involves the buttock and intertriginous areas after systemic exposure to the offending drug and is previously known as baboon syndrome. SDRIFE related with traditional Chinese medicine (TCM) has not been reported. OBJECTIVE: We presented a case of SDRIFE /baboon syndrome induced by TCM, Xi-Huang capsule. METHODS: A 57-years-old man presented with macular erythematous rash mainly on his intergluteal, inguinal, axillary, popliteal regions for a duration of 5 days. The lesions appeared a day after an oral Chinese patent medicine Xi-Huang capsule for arthralgia. Drug eruption was diagnosed. The rash disappeared completely within a week with immediate discontinuation of Xi-Huang capsule and a short term of systemic therapy with glucocorticosteroids. Patch testing was performed on the patient 1 month after complete resolution. He was patch tested with Xi-Huang capsule (5% and 10% in petroleum) using Finn Chambers on Scanpor tape and T.R.U.E. test system. Five heathy volunteers were also patch tested with the same Xi-Huang capsule. RESULTS: Patch testing to 20 common contact allergens including nickel and fragrance were negative. TCM patch test was positive. No positive results were found in five volunteers. Months later, the patient relapsed after an oral herbal Chinese medicine challenge for arthralgia. To avoid the rash recurrence, he stopped taking any Chinese herbal medicine and had complete resolution of disease. CONCLUSION: The Chinese patent drugs for external and oral have unique advantages and have been widely used in many diseases. It is important that dermatologists monitor for clinically significant manifestations of TCM, such as baboon syndrome. Patch testing could help make a definitive diagnosis.

Epidemiology and risk factors for the development of cutaneous toxicities in patients treated with immune-checkpoint inhibitors: A United States population-level analysis.

BACKGROUND: A variety of dermatoses have been reported in the growing number of patients treated with immune-checkpoint inhibitors (ICIs), but the current understanding of cutaneous immune-related adverse events (irAEs) is limited. OBJECTIVE: To determine the cumulative incidence, distribution, and risk factors of cutaneous irAEs after ICI initiation. METHODS: This was a retrospective cohort study of patients in a national insurance claims database including cancer patients treated with ICIs and matched controls. RESULTS: The study included 8637 ICI patients and 8637 matched controls. The overall incidence of cutaneous irAEs was 25.1%, with a median onset time of 113 days. The ICI group had a significantly higher incidence of pruritus, mucositis, erythroderma, maculopapular eruption, vitiligo, lichen planus, bullous pemphigoid, Grover disease, rash, other nonspecific eruptions, and drug eruption or other nonspecific drug reaction. Patients with melanoma and renal cell carcinoma and those receiving combination therapy were at a higher risk of cutaneous irAEs. LIMITATIONS: Retrospective design without access to patient chart data. CONCLUSIONS: This study identifies cutaneous irAEs in a real-world clinical setting and highlights patient groups that are particularly at risk. The results can aid dermatologists at the bedside in the diagnosis of cutaneous irAEs and in formulating management recommendations to referring oncologists regarding the continuation of ICI therapy.

Maculopapular Drug Eruption Caused by Apalutamide: Case Report and Review of the Literature.

Apalutamide, an oral androgen receptor signaling inhibitor, is approved for the treatment of non-metastatic castration-resistant prostate cancer and metastatic prostate cancer. In the international randomized placebo-controlled clinical trials, apalutamide was associated with a higher rate of rash than placebo. However, given that reports from a dermatological perspective are limited, the skin manifestations and histopathology of the skin lesions caused by apalutamide are largely unknown. Here, we report a case of apalutamide-induced drug eruption. A 66-year-old man developed itchy maculopapular erythema on the trunk and extremities 10 weeks after starting apalutamide for progressive prostate cancer. A biopsy specimen showed interface dermatitis with perivascular lymphocytic infiltration in the upper dermis. The lymphocyte transformation test was positive for apalutamide. The skin manifestations improved after discontinuation of apalutamide and treatment with topical corticosteroids and systemic prednisolone. A review of the dermatology literature on apalutamide-induced drug eruption yielded only six cases, including our case. Dermatologically, there were four cases of maculopapular rash and two of toxic epidermal necrolysis and histopathologically, there were three cases of interface dermatitis, two of epidermal necrosis, and one of spongiotic dermatitis. Four patients had peripheral eosinophilia. A lymphocyte transformation test was performed in three cases and was positive for apalutamide in all cases. Except for the two cases of toxic epidermal necrolysis, which were fatal, the skin eruptions appeared 10 weeks after starting apalutamide. Considering the increasing number of patients with prostate cancer being treated with apalutamide, cases of apalutamide-induced drug eruption need to be accumulated and analyzed.

ACC1-expressing pathogenic T helper 2 cell populations facilitate lung and skin inflammation in mice.

T cells possess distinguishing effector functions and drive inflammatory disorders. We have previously identified IL-5-producing Th2 cells as the pathogenic population predominantly involved in the pathology of allergic inflammation. However, the cell-intrinsic signaling pathways that control the pathogenic Th2 cell function are still unclear. We herein report the high expression of acetyl-CoA carboxylase 1 (ACC1) in the pathogenic CD4+ T cell population in the lung and skin. The genetic deletion of CD4+ T cell-intrinsic ACC1 dampened eosinophilic and basophilic inflammation in the lung and skin by constraining IL-5 or IL-3 production. Mechanistically, ACC1-dependent fatty acid biosynthesis induces the pathogenic cytokine production of CD4+ T cells via metabolic reprogramming and the availability of acetyl-CoA for epigenetic regulation. We thus identified a distinct phenotype of the pathogenic T cell population in the lung and skin, and ACC1 was shown to be an essential regulator controlling the pathogenic function of these populations to promote type 2 inflammation.

Urticaria and edema in a 2-year-old boy.

The absence of blisters, the presence of mild systemic symptoms, and the patient's age guided the diagnosis.