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.

Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways.

PURPOSE: Immune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood. EXPERIMENTAL DESIGN: Phenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. RESULTS: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine-targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. CONCLUSIONS: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.

Multi-center retrospective review of vitiligo-like lesions in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors.

PURPOSE: Cutaneous adverse effects from cyclin-dependent 4 and 6 kinase inhibitors (CDK4/6i) used in metastatic breast cancer are prevalent and well described. Vitiligo-like lesions have been reported and are rare. They can negatively impact patients' quality of life and may be associated with survival benefits. We describe the clinical characteristics of vitiligo-like lesions in an international cohort of patients treated with CDK4/6i to help improve recognition and management. METHODS: Retrospective review of patients diagnosed with vitiligo-like lesions from CDK4/6i from five academic institutions in the USA and Europe was performed. Ten patients were included in the study. RESULTS: Median age of our patients was 55 (range 37-86). Median progression-free survival was 24 months in 5 patients. The median time to rash was 10 months. Sun-exposed areas such as the arms and face were the most affected areas. Multiple skin-directed therapies such as topicals, laser, and phototherapy were trialed with minor success. Mild repigmentation was seen in one patient treated with ruxolitinib cream. CDK4/6 treatment was discontinued due to the vitiligo-like lesions in one patient. CONCLUSION: Clinical characteristics are similar to previously reported findings in case reports and series. We add topical ruxolitinib as a potential treatment option for these patients and include data regarding progression-free survival that should continue to be collected. No definitive conclusions can be made regarding survival benefits from our cohort. Clinicians should refer these patients to dermatologists to aid with management.

Effect of a Home-based Walking Intervention on Cardiopulmonary Fitness and Quality of Life Among Men with Prostate Cancer on Active Surveillance: The Active Surveillance Exercise Randomized Controlled Trial.

BACKGROUND: Active surveillance (AS) is standard care for most men with low-risk prostate cancer (PC); yet, many men on AS eventually undergo curative therapy. Interventions to lower the risk of cancer progression and fear of recurrence among men on AS for PC are needed. OBJECTIVE: To determine the effect of aerobic exercise on cardiorespiratory fitness, body size, and quality of life (QOL) among men on AS for PC. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 1:1 randomized controlled trial among 51 men with low-risk PC who elected AS. Participants were enrolled at the University of California, San Francisco. INTERVENTION: The 16-wk intervention included a home-based walking program with a nonlinear exercise prescription tailored to baseline fitness level, heart rate monitor, and weekly phone call with an exercise physiologist. Controls received printed materials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cardiorespiratory fitness was measured using VO2peak; secondary outcomes included change in body size, anxiety, and QOL. Analyses were based on intention to treat. RESULTS AND LIMITATIONS: Between 2016 and 2021, we randomized 51 men to intervention (n = 26) or control (n = 25). Follow-up was 88% (45/51), 85% (22/26) in the intervention and 92% (23/25) in the control group. At 16 wk, the intervention group had a higher mean VO2peak than the control group (31.9 ± 4.7 vs 27.2 ± 4.8 ml/kg/min; group × time effect p value: <0.001). Additionally, the intervention group reported less fear of PC recurrence and urinary obstruction/irritation, while controls reported more of these two QOL measures, from 0 to 16 wk (p = 0.04 and 0.03, respectively). Two participants discontinued the intervention, including one due to knee pain related to the study. CONCLUSIONS: A home-based walking program improved VO2peak and reduced urinary obstruction/irritation and fear of recurrence among men on AS for PC. PATIENT SUMMARY: Moderate to vigorous aerobic exercise improves fitness and quality of life among men on active surveillance for prostate cancer.

Management of Neovaginal Secretions After Salvage Gender Affirming Right-Colon Vaginoplasty Using Glycopyrrolate.

Purpose: We report a novel case of a transgender woman who experienced excess mucosal secretion leading to symptomatic skin irritation after her colonic vaginoplasty successfully treated with glycopyrrolate. Methods: This is a case report of a 47-year-old transgender woman with symptomatic excess mucosal secretion and skin irritation from colonic vaginoplasty, and we describe her treatment course and responses. Patient consent was obtained for publication. Results: The patient's chronic neovaginal discharge improved with glycopyrrolate. Conclusions: Anticholinergic drugs may be helpful in treating patients who experience chronic neovaginal discharge following colonic vaginoplasty.

Biologic Therapies in HIV/AIDS Patients with Inflammatory Diseases: A Systematic Review of the Literature.

Biologic therapies have been increasingly developed and used for the treatment of severe inflammatory diseases. However, the safety and efficacy profile of biologic drugs in patients with HIV is not well established as this patient population is historically excluded from clinical trials. We review the available evidence of biologic use in people with HIV. We conducted a systematic review of the literature up to June 29, 2022 and included studies that treated patients with HIV who have inflammatory disease using biologic drugs. Clinical data regarding safety and efficacy were abstracted into tables. One hundred twelve studies were included, and 179 patients were included in our study. Nearly all classes of biologics drugs had a favorable safety profile with minimal or minor adverse events. Anti-CD-20 inhibitors and TNF-alpha inhibitors were associated with opportunistic infections. Transient increase in HIV viral load was noted with use of some agents such as TNF-alpha inhibitors. The quality of evidence is low, restricted to case reports and retrospective reviews. However, the safety profile of biologics observed in these patients with HIV was overall favorable.

Quality of life for men with metastatic castrate-resistant prostate cancer participating in an aerobic and resistance exercise pilot intervention.

BACKGROUND: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood. METHODS: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated using self-reported questionnaires (e.g., QLQ-C30, PROMIS Fatigue, Pittsburgh Sleep Quality Index (PSQI), EPIC-26) collected at baseline and 12 weeks. RESULTS: A total of 25 men were randomized (10 control, 8 aerobic, 7 resistance). Men were predominately white (76%) with a median age of 71 years (range: 51-84) and 10.5 years (range: 0.9-26.3) post prostate cancer diagnosis. The men reported poor sleep quality and high levels of fatigue at enrollment. Other baseline QoL metrics were relatively high. Compared to the controls at 12 weeks, the resistance arm reported some improvements in social function and urinary irritative/obstruction symptoms while the aerobic arm reported some improvements in social function and urinary incontinence, yet worsening nausea/vomiting. Compared to the resistance arm, the aerobic arm reported worse urinary irritative/obstruction symptoms and self-rated QoL, yet some improvements in emotional function, insomnia, and diarrhea. CONCLUSIONS: The 3-month exercise intervention pilot appeared to have modest effects on QoL among mCRPC survivors on ADT. Given the feasibility, acceptability, and safety demonstrated in prior analyses, evaluation of the effect of the intervention on QoL in a larger sample and for extended duration may still be warranted.

Feasibility, safety, and acceptability of a remotely monitored exercise pilot CHAMP: A Clinical trial of High-intensity Aerobic and resistance exercise for Metastatic castrate-resistant Prostate cancer.

BACKGROUND: Exercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: We conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high- and moderate-intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews. RESULTS: Between March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty-three men (82%) completed the 12-week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others. CONCLUSIONS: Remotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer.