Erythema dyschromicum perstans-like eruptions induced by epidermal growth factor receptor inhibitors in patients with lung cancer.

INTRODUCTION: Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition. METHODS: We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study. RESULTS: The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.

The "Flolan Rash": An Impressively Asymptomatic and Non-Inflammatory Eruption Following Long-Term Epoprostenol Therapy.

Epoprostenol (Flolan) is a last-resort intravenous medication for the treatment of severe pulmonary arterial hypertension (PAH). Cutaneous adverse events of Flolan are well-known by pulmonologists, though lacking in dermatologic literature. We report a near erythrodermic appearing, yet asymptomatic eruption lasting 10 years in a woman with end-stage PAH treated with long-term intravenous epoprostenol. Non-pruritic, blanching, erythematous papules coalescing to plaques surrounded by a hypopigmented halo encompassed her entire torso, as well as bilateral upper and lower extremities. Additional findings included bright red palms and soles associated with pain and tingling while walking. Laboratory workup revealed thrombocytopenia and a slightly elevated erythrocyte sedimentation rate (ESR); connective tissue disease markers were negative. Skin biopsies were, surprisingly, largely unremarkable without an inflammatory infiltrate. The patient was trialed on topical clobetasol ointment without effect. Her striking, yet asymptomatic and non-inflammatory eruption was thought due to long-term use of epoprostenol, a last-resort synthetic prostacyclin used to treat severe PAH. As her cutaneous findings were not bothersome, her dose of Flolan was not lowered and her lower extremity pain was treated with gabapentin. With this case, we aim to increase awareness of the impressive “Flolan rash”, a persistent erythematous eruption well-known by pulmonologists, yet scarcely described in dermatologic literature. Significant Finding: We report a striking, yet asymptomatic and non-inflammatory skin eruption lasting 10 years presumed due to long-term use of epoprostenol for end-stage pulmonary arterial hypertension. Meaning: Cutaneous adverse events of intravenous epoprostenol are well-known by pulmonologists, though lacking in dermatologic or primary care literature. The extensive body surface involvement, and near erythroderma, associated with Flolan necessitates awareness by patients, dermatologists, and other healthcare providers outside of the field of pulmonology. J Drugs Dermatol. 2022;21(11):1249-1251. doi:10.36849/JDD.6821.

Diffuse cutaneous mastocytosis: Case report and literature review.

A 6-month-old boy was referred to our burn unit with a recurrent bullous dermatitis, fever, and emesis, originally diagnosed as staphylococcal scalded skin syndrome (SSSS) at an outside hospital. Infectious workup was negative and shave biopsy revealed a dense, diffuse dermal infiltrate of mast cells, consistent with diffuse cutaneous bullous mastocytosis-a rare variant of cutaneous mastocytosis. Treatment included a prolonged course of corticosteroids and antihistamines. Recognition of this rare form of mastocytosis is important, as it can be easily mistaken for other pediatric bullous diseases and is associated with life-threatening complications including vasodilation, anaphylactic shock, gastrointestinal bleeding, and death.

Trichoscopic features of tinea capitis in a straight-haired Hispanic woman.

Comma and corkscrew hairs are trichoscopic markers of tinea capitis. Although comma hairs have been reported in both black and white patients with tinea capitis, corkscrew hairs were previously hypothesized to manifest exclusively in patients with curly or African hair types. However, we report a significant number of comma and corkscrew hairs in a Hispanic female patient with naturally straight hair and Trichophyton tonsurans tinea capitis. Thus, dermoscopy is a rapid, noninvasive, and cost-effective tool for evaluating tinea capitis and should be used in combination with culture in all patients regardless of hair texture or race.

Scrotal Melanoma: A Systematic Review of Presentation, Treatment, and Outcomes.

BACKGROUND: Primary male genital melanomas are rare. Of these, scrotal melanoma is the least common, and is unfortunately often detected late in the disease course. OBJECTIVE: To assess the clinical presentation, treatment modalities, and outcome of scrotal melanoma to aid clinician management. METHODS: Systematic literature review of PubMed, yielding 23 cases, of which 20 met the inclusion criteria. RESULTS: Although previously thought to have the best outcome of genitourinary melanomas, scrotal melanomas are associated with high mortality and late presentation. Scrotal melanoma presented as Stage I/II disease 18.75% of the time, Stage III 56.3% of the time, and Stage IV 25% of the time, whereas typical cutaneous melanoma presents as Stage I/II disease 84% of the time, Stage III 8% of the time, and Stage IV 4% of the time. Half of patients experienced recurrence of their disease. All patients who presented with metastases to distant organs died. LIMITATIONS: Small sample size. Few cases described a Breslow's depth making it difficult to draw conclusions on tumor thickness and survival outcome. CONCLUSION: Scrotal melanoma is rare, aggressive, and is often caught late in the disease course. The authors encourage dermatologists to educate patients and destigmatize genital lesions to increase the likelihood of earlier detection and better patient outcomes.

Genital melanoma: are we adequately screening our patients?

Full-body skin exams (FBSE) play an integral role inearly detection and treatment of skin cancer. Promptdetection of melanoma is especially importantas survival outcomes decrease significantly withpresentation of advanced disease. Given thatmelanoma may grow in areas of skin with little to nosun exposure, genital melanomas are a recognizedentity in cutaneous oncology.

Osimertinib tolerance in a patient with Stevens Johnson syndrome during osimertinib therapy after treatment with pembrolizumab.

BACKGROUND: Osimertinib has emerged as an important tool in the treatment of non-small cell lung cancers (NSCLC) with certain activating mutations of epidermal growth factor receptor (EGFR). However, Osimertinib may cause adverse effects, including severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk of certain adverse effects may be increased in the setting of recent use of immune checkpoint inhibitor (ICI) therapy, although it is unclear whether recent use of ICI therapy is a risk factor for Osimertinib-induced SJS specifically. CASE PRESENTATION: We present a patient with EGFR L858R mutation-positive metastatic NSCLC who developed Osimertinib-induced SJS after recent administration of eight cycles of a pembrolizumab-containing chemotherapy regimen. Osimertinib, which was the best treatment targeting his lung cancer, was avoided due to history of SJS. Four years later, because of unresponsiveness or side effects of alternative treatments, he underwent Osimertinib challenge and tolerated it. CONCLUSION: This case highlights the importance of multi-disciplinary care and supports the hypothesis that the risk of SJS to Osimertinib is significantly higher in the context of recent administration of ICI therapy and, patients may tolerate Osimertinib after certain time has elapsed after the last dose of ICI.

Relapse of Plasmablastic Lymphoma With Cutaneous Involvement in an Immunocompetent Male.

Plasmablastic lymphoma (PBL) is a rare type of non-Hodgkin lymphoma frequently found in the context of immunosuppression and infection with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV). A 33-year-old immunocompetent male presented with recurrent episodes of epistaxis and a growing intranasal mass. Excisional biopsy of the mass revealed an immunohistochemical profile diagnostic of PBL. Upon completion of chemoradiation, he underwent a transnasal endoscopic mucosal flap tissue rearrangement to restore patency for both functional and surveillance purposes. There was no endoscopic evidence of residual or recurrent disease. However, 8 months later, he was found to have a relapse involving the skin. The nasal cavity is one of the most common sites affected by PBL. Involvement of the nasal cavity may present with symptoms of persistent epistaxis accompanied by an enlarging mass. A plasmablastic immunophenotype in combination with HIV or EBV positivity can aid diagnosis.

The banned sunscreen ingredients and their impact on human health: a systematic review.

Recent evidence of high systemic absorption of sunscreen ingredients has raised concerns regarding the safety of sunscreen products. Oxybenzone (BP-3) and octinoxate (OMC), two common sunscreen ingredients, were recently banned in Key West and Hawaii owing to their toxic effects on marine ecosystems. Their impact on human health requires a careful assessment. To summarize the current evidence on the association between the systemic level of BP-3 or OMC and its health impact, a primary literature search was conducted using PubMed database in February 2019. There are 29 studies that address the impact of these ingredients on human health. Studies show that elevated systemic level of BP-3 has no adverse effect on male and female fertility, female reproductive hormone level, adiposity, fetal growth, child's neurodevelopment, and sexual maturation. However, the association of BP-3 level on thyroid hormone, testosterone level, kidney function, and pubertal timing has been reported and prompts further investigations to validate a true association. The systemic absorption of OMC has no reported effect on thyroid and reproductive hormone levels. In conclusion, current evidence is not sufficient to support the causal relationship between the elevated systemic level of BP-3 or OMC and adverse health outcomes. There are either contradictory findings among different studies or an insufficient number of studies to corroborate the observed association. To accurately evaluate the long-term risk of exposure to BP-3 and OMC from sunscreen, a well-designed longitudinal randomized controlled trial needs to be conducted.

Non-invasive optical biopsy by multiphoton microscopy identifies the live morphology of common melanocytic nevi.

Multiphoton microscopy (MPM) is a promising non-invasive imaging tool for discriminating benign nevi from melanoma. In this study, we establish a MPM morphologic catalogue of common nevi, information that will be critical in devising strategies to distinguish them from nevi that are evolving to melanoma that may present with more subtle signs of malignancy. Thirty common melanocytic nevi were imaged in vivo using MPM. Quantitative parameters that can distinguish between different types of nevi were developed and confirmed by examining the histology of eleven of the imaged nevi. MPM features of nevi examined included cytologic morphology of melanocytes in the epidermis and dermis, the size and distribution of nevomelanocytes both within and around nests, the size of rete ridges, and the presence of immune cells in the dermis. Distinguishing features include cytological morphology, the size of nevomelanocytes, the size of nevomelanocyte nests, and the distribution of nevomelanocytes. Notably, these distinguishing characteristics were not easily appreciated in fixed tissues, highlighting essential differences in the morphology of live skin. Taken together, this work provides a morphologic compendium of normal nevi, information that will be critical in future studies directed at identifying melanocytic nevi that are evolving to melanoma.

Foscarnet-Induced Penile Ulceration.

This case report describes an uncircumcised male individual with tender perimeatal erythema and ulceration extending to the right glans.