Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions: Current and Future Trends

Childhood Vitiligo Abstract Vitiligo is a common acquired depigmenting skin disease characterized by a progressive loss of functional melanocytes. It may appear from the first years of life to late adulthood. Childhood vitiligo (CV), defined as vitiligo that begins before the age of 12 years, is common and may differ from post-CV in terms of epidemiology, clinical presentation, comorbidities, and treatment options. Taking into consideration the potential significant psychosocial impact of the disease on both children and their parents, all available therapeutic options must be offered to patients who desire treatment. According to the most recent guidelines, topical corticosteroids, topical calcineurin inhibitors, and narrowband ultraviolet B phototherapy are the most commonly used treatment modalities for vitiligo in children. This review presents recent data regarding the whole spectrum of CV. Differences between CV and post-CV are also discussed.

Is There a Role for Antiandrogen Therapy for Hidradenitis Suppurativa? A Systematic Review of Published Data Abstract Background Hidradenitis suppurativa/acne inversa is a disease with deep-seated chronic painful nodules, abscesses, and draining sinus tracts, which manifests on the apocrine gland-rich skin areas of the body. Observational findings demonstrate that the disease usually appears after puberty, exhibits pre-menstrual flares in women, improves in pregnancy, and worsens post-partum, which indicates a role of hormones and particularly of androgens in its pathophysiology. Because increased androgen levels in serum have not been widely reported, an end-organ androgen hypersensitivity has been postulated. Objective The aim of this systematic review was to identify and present evidence for antiandrogen therapeutic options for the treatment of hidradenitis suppurativa/acne inversa. Methods A literature search was conducted in different medical electronic databases using the keywords “hidradenitis”, “suppurativa”, “acne inversa”, and “antiandrogen” on 1 December, 2018. The main therapeutic options were subsequently used as separate keywords with the disease terms in a separate search. Results The main therapeutic options yielded were cyproterone acetate, spironolactone, finasteride, and metformin. One randomized controlled crossover trial and seven case series were identified following use of a standard extraction form for eligibility. Conclusion The existing studies do not allow a robust evidence-based recommendation for the use of antiandrogens in the treatment of hidradenitis suppurativa/acne inversa. Further randomized controlled trials are needed to define the role of hormonal treatment as an alternative or concomitant therapy together with antibiotics or biologics.

Immune Checkpoint Inhibitors for Treating Advanced Cutaneous Squamous Cell Carcinoma Abstract Cutaneous squamous cell carcinoma (CSCC) is one of the most common human malignancies, and the incidence is increasing with time. High mutational loads, known infiltration with lymphocytes, and programmed death (PD)-ligand 1 (PD-L1) expression suggest that immune checkpoint inhibitors, such as PD-1 inhibitors, may show utility in treating CSCC, similar to response see in other solid tumor types. Recently, the robust responsiveness of CSCCs to the PD-1 inhibitor cemiplimab was revealed in the results of a combined phase I/II clinical trial, with an overall response rate of 50% and a durable response exceeding 6 months in 57% of responders. Compared to prior systemic therapies with scant data for efficacy and safety, cemiplimab is a breakthrough therapy, the first systemic drug approved for advanced CSCCs. Other immune checkpoint inhibitors have shown promise through case reports and series, and are currently in clinical development for CSCCs.

Quality-of-Life Research in Acne Vulgaris: Current Status and Future Directions Abstract Acne patients may have significant quality-of-life (QoL) impairment, therefore assessment of health-related QoL (HRQoL) in acne patients is recommended by several national and international guidelines as an integral part of acne management. The inclusion of QoL assessment in core outcome sets is now a popular idea. Several acne-specific QoL questionnaires are available but none cover all topics presented in other instruments. The impact of acne on different aspects of QoL may vary between patients from different age groups. The European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes has initiated a study on the relevance of the different QoL topics in acne patients. Detailed recommendations on treatment goals and changes of treatment approaches based on a validated banding system and a minimal clinically important difference in HRQoL questionnaires (such as the Dermatology Life Quality Index) may be an important and promising approach.

Autoinflammatory Disorders: A Review and Update on Pathogenesis and Treatment Abstract The autoinflammatory diseases comprise a broad spectrum of disorders characterized by unchecked activation of the innate immune system. Whereas aberrations in adaptive immunity have long been identified in ‘autoimmune’ disorders, the concept of ‘autoinflammation’ emerged relatively recently, first describing a group of clinical disorders characterized by spontaneous episodes of systemic inflammation without manifestations typical of autoimmune disorders. Improved knowledge of innate immune mechanisms, coupled with remarkable progress in genomics and an expanding number of clinical cases, has since led to an increasing number of disorders classified as autoinflammatory or containing an autoinflammatory component. Biologic therapies targeting specific components of the innate immune system have provided immense clinical benefit, and have further elucidated the role of innate immunity in autoinflammatory disorders. This article reviews the basic mechanisms of autoinflammation, followed by an update on the pathophysiology and treatment of the monogenic and multifactorial autoinflammatory diseases, and the common dermatologic conditions in which autoinflammation plays a major role.

Special Considerations in the Treatment of Mycosis Fungoides Abstract Mycosis fungoides is the most common form of cutaneous T cell lymphoma. Although normally presenting to physicians at an early stage and with an indolent course, mycosis fungoides can have a varied presentation. The National Comprehensive Cancer Network (NCCN) has created guidelines for the treatment and staging of mycosis fungoides. Although comprehensive, in practice these guidelines do not provide specific treatment regimens for lesions located in difficult locations and those recalcitrant to the recommended therapy. Because of this, suggestions based on the practices and decisions made at the multidisciplinary cutaneous lymphoma clinic at the Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA, are presented here. Lesions located in areas such as the face and intertriginous zones are often challenging to treat because first-line therapies are often inappropriate, with the locations increasing the possibility of side effects. Additionally, lesions located in the bathing suit distribution are often nonresponsive to first-line therapies for reasons still undetermined. Finally, although well-described, erythroderma secondary to mycosis fungoides is challenging to treat, with controversy surrounding various methods of control. This article both highlights difficult clinical scenarios and reviews the recommended treatment as provided by the NCCN guidelines and provides alternative therapy for lesions that are either difficult to treat because of the location or are recalcitrant to the recommended therapy. With suggestions for the apparent gaps in guidelines, providers can better treat patients who present with more complicated conditions.

Management Recommendations for Dupilumab Partial and Non-durable Responders in Atopic Dermatitis Abstract As the first targeted systemic agent for the treatment of moderate to severe atopic dermatitis (AD), dupilumab represents a novel therapeutic opportunity for both patients and providers. However, a subset of patients receiving dupilumab are either partial responders who exhibit some improvement in Investigator’s Global Assessment score but not sufficient to meet the primary endpoint, or are non-durable responders who achieve therapeutic endpoint with subsequent partial loss of efficacy. We propose a therapeutic algorithm for the management of dupilumab partial responders and non-durable responders that involves maximizing topical therapy, seeking alternative diagnoses, and using dupilumab in conjunction with traditional systemic immunosuppressive agents. With a number of targeted agents for AD in the drug development pipeline, we encourage patients who do not have an adequate response to dupilumab to remain patient and optimistic as the arsenal of AD treatment modalities continues to expand.

Association of Early Systemic Corticosteroid Therapy with Mortality in Patients with Stevens–Johnson Syndrome or Toxic Epidermal Necrolysis: A Retrospective Cohort Study Using a Nationwide Claims Database Abstract Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatologic disorders with high mortality. The role of systemic corticosteroids as an adjunctive therapy for SJS or TEN remains controversial. Objective The aim of this study was to determine whether treatment with early systemic corticosteroids impacts the in-hospital mortality of patients hospitalized with SJS or TEN. Methods Using the Japanese Diagnosis Procedure Combination Database, a large nationwide inpatient administrative claims database, we identified inpatients aged ≥ 18 years who were admitted with SJS or TEN. Treatment with early systemic corticosteroids was defined as starting treatment with systemic corticosteroids within 2 days (day 0 or day 1) of admission. The primary outcome was in-hospital mortality. We examined the association between early systemic corticosteroids and in-hospital mortality using propensity score (PS) analyses. Results We identified 1846 eligible patients with SJS or TEN, including 793 patients with early systemic corticosteroid use at ≤ 2 mg/kg/day, 558 patients with early systemic corticosteroid use at > 2 mg/kg/day, and 495 patients without early corticosteroid use. PS matching created 235 pairs (> 2 mg/kg/day vs. controls) and 332 pairs (≤ 2 mg/kg/day vs. controls). Early systemic corticosteroid use was not significantly associated with lower in-hospital mortality by PS matching (> 2 mg/kg/day vs. controls: relative risk [RR] 0.83, 95% confidence interval [CI] 0.37–1.85; ≤ 2 mg/kg/day vs. controls: RR 0.61, 95% CI 0.28–1.36) and by inverse probability of treatment weighting (> 2 mg/kg/day vs. controls: RR 0.99, 95% CI 0.45–2.19; ≤ 2 mg/kg/day vs. controls: RR 0.65, 95% CI 0.29–1.47). Conclusion Early systemic corticosteroid therapy for patients with SJS or TEN was not associated with lower in-hospital mortality. Further studies are needed to define the effect of corticosteroids for patients with SJS or TEN.

Effect of Biological Treatment on Fatigue in Psoriasis: A Systematic Review and Meta-Analysis Abstract Background Fatigue is frequent in patients with psoriasis. Though conventional drugs in general have no effect on fatigue, biological agents have demonstrated beneficial effects in several other chronic inflammatory diseases. Objective The objective of the present study was to evaluate the effect of biological drugs on fatigue in patients with psoriasis vulgaris. Methods We conducted a meta-analysis of randomized controlled trials in which anti-interleukin-12/23, anti-interleukin-23, anti-interleukin-17, or anti-tumor necrosis factor-α agents were used for psoriasis vulgaris and fatigue was an outcome measure. Results A total of eight randomized controlled trials fulfilled criteria for inclusion in the meta-analysis. The studies used two fatigue reporting scales: the Functional Assessment of Chronic Illness Therapy-Fatigue and the Short Form 36 Health Survey Vitality Subscale. Treatment by biological agents in general compared with placebo led to a significant reduction in fatigue, with a standardized mean difference of − 0.40 (95% confidence interval − 0.46 to − 0.34; p < 0.001). Conclusion Biological drugs used for the treatment of psoriasis vulgaris have a consistently small-to-moderate beneficial effect on fatigue independent of the type of drug.