Dipeptidyl peptidase-4 inhibitor-associated cutaneous eruptions: a retrospective observational study.

BACKGROUND: Dipeptidyl peptidase (DPP)-4 plays a complex role in immune regulation and its inhibition can have effects on the pathogenesis of various skin diseases. Studies have shown that DPP-4 inhibitors are associated with an increased risk of bullous pemphigoid (BP). AIM: To analyse the clinical and histopathological features of cutaneous adverse events in patients on DPP-4 inhibitors. METHODS: We performed a retrospective review of patients with suspected DPP-4 inhibitor-associated cutaneous adverse events, at a tertiary teaching hospital from 1 January 2017 to 31 December 2020. Exclusion criteria included previous history of chronic skin disease and lack of histopathological reports or follow-up records. The clinical characteristics, latency period, Naranjo Adverse Drug Reaction Probability Scale and clinical outcomes were evaluated. RESULTS: In total, 18 patients (10 men, 8 women; mean age 68.6 years, range 38-89 years) were included. The DPP-4 inhibitors used were teneligliptin (n = 6), vildagliptin (n = 6), sitagliptin (n = 4), linagliptin (n = 1) and saxagliptin (n = 1). The mean interval between therapy initiation and lesion onset was 8.8 months (range 1-24 months). The dermatoses noted were BP (n = 12; 66.6%), lichenoid dermatitis (n = 4; 22.2%), psoriasiform dermatitis (n = 1; 5.6%) and spongiotic dermatitis (n = 1; 5.6%). Eight patients (44.4%) had necrotic keratinocytes as one of the distinct histological features. Causality assessment using the Naranjo scale rated the causative role of DPP-4 inhibitors as 'possible' in all patients. Of the 18 patients, 11 (61.1%) noted improvement in their condition following discontinuation of DPP-4 inhibitors, with 5 having complete remission within 6 months of stopping the drug. CONCLUSION: DPP-4 inhibitor-associated dermatoses are not necessarily limited to BP. It is necessary to recognize the possibility of other dermatoses in patients on DPP-4 inhibitors as drug substitution/cessation may improve disease morbidity.

Characterization and Prognostic Significance of Cutaneous Immune-Related Adverse Events in Indian Patients on Immune Checkpoint Inhibitor Therapy.

INTRODUCTION: Cutaneous immune-related adverse-events (cIRAEs), commonly seen in cancer patients receiving immune checkpoint inhibitors (ICI) are reported to be associated with better patient survival; however, they have seldom been studied in Indian population. Recent reports suggest racial differences in IRAEs and also in survival outcomes. OBJECTIVES: To study the various cIRAEs in Indian patients on ICI therapy and to analyze the association between cIRAEs and patient survival outcomes. METHODS: We conducted a retrospective cohort study of 86 cancer patients receiving immunotherapies in a tertiary care hospital in India and studied incidence, nature and grades of cutaneous immune-related adverse events and the association of cIRAEs with the patient survival outcomes. RESULTS: Eighty-six patients were included, of whom 16 patients (18.6%) developed cIRAEs, with pruritus (12.8%) and maculopapular eruption (8.1%) being the most common. Kaplan-Meier plot with log-rank test showed that patients developing any type of cIRAE had longer progression-free survival than those without (P = 0.023) and a better objective-response-rate (50% versus 18.5%, P = 0.008). CONCLUSIONS: Most common cIRAEs in our study were pruritus and maculopapular rash. The incidence of cIRAEs was lower in our Indian cohort compared to that reported in Caucasian cohorts. Development of cutaneous immune-related adverse event in cancer patients on ICI was associated with a longer progression-free-survival and a better objective-response-rate. Thus, cIRAEs may serve as a surrogate marker for better patient outcomes.

Ribociclib-induced extensive vitiligo-like lesions: possible pathomechanisms with clinical, dermoscopic and histological correlation.

Cyclin dependent kinase (CDK) 4/6 inhibitors are targeted agents which act on cyclin-D and these combined with hormonal therapy have been approved for the treatment of locally advanced or metastatic breast cancer. CDK 4/6 inhibitors have been found to have a tolerable adverse event profile; however, they have been associated with various dermatological adverse events. We report a case of ribociclib-induced vitiligo and discuss the clinical, dermoscopic and histological features with a review of the various possible pathomechanisms involved.

Tofacitinib in the treatment of refractory eczemas - a case series.

Janus Kinase inhibitors have been shown to be effective in the treatment of various dermatoses such as alopecia areata, psoriasis, vitiligo and atopic dermatitis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is a common junction for the signaling of several dermatologically significant cytokines and the inhibition of this pathway by JAK inhibitors may be broadly useful in the treatment of various other dermatological disorders. A case series is presented of twelve patients (M:6, F:6) with a mean age 47.1 years, presenting with various eczematous dermatoses (histopathology showing spongiotic dermatitis) who had failed to respond to conventional therapy. These patients were prescribed tofacitinib. All 12 patients improved and 10 patients had improvement to clear or almost clear (physician global assessment score 0/1) after 1 month of therapy. No hematological or biochemical abnormalities were noted during the treatment period. Infections were the most common adverse events observed. Conventional treatment options like systemic steroids and steroid sparing agents are the cornerstone in the treatment of chronic eczematous disorders, however, in patients who do not respond to conventional agents, tofacitinib may represent a viable treatment option.