American Journal of Clinical Dermatology

The number of solid organ transplants has been increasing annually worldwide. Advances in transplantation surgery and community awareness of organ donation have been key contributors. Combined with increased understanding of immunosuppression, there are a growing number of solid organ transplant recipients in the community as a result of improved long-term outcomes. There remains a high incidence of deaths worldwide post-transplant due to non-melanoma skin cancer (NMSC), which has greater morbidity and mortality in this population than in the general community. Many transplant candidates are not screened prior to organ transplantation and not followed up dermatologically after transplant. After a comprehensive review of the MEDLINE database, we present an update of literature on risk factors for melanoma and non-melanoma skin cancer development in transplant recipients. Medications used by transplant recipients, including immunosuppressants and antibiotics, are discussed along with their respective risks of skin cancer development. We conclude with evidence-based recommendations for models of care, including patient education and dermatological review of transplant recipients.

Purpose: To summarize success rates of the topical calcineurin inhibitors tacrolimus and pimecrolimus in treating atopic dermatitis. Methods: Randomized controlled trials (RCTs) comparing either drug to themselves (i.e. dose-ranging studies), each other, the vehicle (or placebo), or corticosteroids were obtained from Medline, EMBASE, and Cochrane databases. Two reviewers identified studies and extracted data, a third reviewer adjudicated disagreements. Outcomes included success, as defined by 90%, 75%, or 50% reductions from baseline in Eczema Area and Severity Index (EASI) scores or equivalent at 1, 3, 6, and 12 months, and also the difference between drug and vehicle (placebo). Rates were combined using a random effects meta-analytic model. Results: Of 180 articles identified, 165 were rejected (142 not RCTs/inappropriate outcome, 23 inappropriate/unextractable data). We included 15 articles reporting on 16 trials (nine tacrolimus and seven pimecrolimus trials) involving a total of 5301 patients, of whom 2107 received tacrolimus, 1225 received pimecrolimus and 1969 patients were controls. Tacrolimus reduced EASI scores by 65.6% at 1 month and 73.0% at 3 months; pimecrolimus reduced scores by 61.5% at 1 month, 60.3% at 6 months, and 61.9% at 12 months. When the difference in EASI score reductions were compared between active drug and placebo, tacrolimus success was 51.5% above placebo at 1 month and pimecrolimus was 45.9% higher at 1 month, 24.9% at 6 months, and 16.1% at 12 months. Conclusions: Success rates for tacrolimus and pimecrolimus were statistically similar. However, tacrolimus rates were consistently higher numerically than those for pimecrolimus, and tacrolimus was used in patients with more severe disease. A head-to-head RCT is required to determine if true differences exist between these drugs.

Generalized pustular psoriasis (GPP) is a rare neutrophilic skin condition characterized by episodes of widespread eruption of sterile macroscopic pustules that can be associated with systemic inflammation. The rarity of GPP and its heterogeneous cutaneous and extracutaneous symptoms pose considerable challenges to the development and adoption of comprehensive accurate disease measures for the routine clinical assessment of disease severity and the evaluation of new treatments in clinical trials. Psoriasis disease measures remain among the most commonly used methods for evaluating patients with GPP, despite their limitations owing to a lack of assessment of pustules (a hallmark of GPP), systemic inflammation, and disease symptoms. The adaptation of psoriasis disease measures and the development of assessment tools specific for GPP severity will enable more effective and accurate monitoring of patients with GPP and enhance the clinical development of new therapies. Further clinical validation of recently developed modified assessment tools, such as the Generalized Pustular Psoriasis Physician Global Assessment and the Generalized Pustular Psoriasis Area and Severity Index, and international consensus on using quantitative tools and patient-reported outcome measures in the development of new treatments are needed to advance patient care.

Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25–85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients’ quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.

Lichen sclerosus is a chronic inflammatory disorder with a propensity to affect the mucocutaneous anogenital area. Topical corticosteroids remain the treatment of choice for this condition and constitute an effective therapeutic modality. However, in patients with corticosteroid-resistant disease, when long-term remission is not sustainable, or in those intolerant to these agents, topical calcineurin inhibitors may be considered. Studies have demonstrated their efficacy and tolerability; however, concerns remain with regard to their malignant potential with long-term use. As lichen sclerosus is a potentially precancerous dermatosis, topical calcineurin inhibitors should be used with caution in this disorder.

Background: Melanotic schwannoma is a pigmented nerve tumor that may be located in the skin and express local aggressivity. This tumor may occur singly. It may also be part of the Carney complex which consists of various, but specific, tumors. Objective: We report two cases of subcutaneous melanotic schwannoma localized on the trunk in two men aged 37 and 45 years. Methods: Conventional histology and immunohistochemistry were performed. Results: One melanotic schwannoma was associated with a cutaneous atypical myxoma and multiple melanocytic lesions, all being part of the Carney complex. The other case had no associated signs. In both cases, the melanotic schwannoma was completely excised and did not recur. Conclusion: Melanotic schwannoma is rare and curable by surgery. It must not be confused with malignant melanoma and other pigmented neoplasms. The Carney complex should be carefully ruled out.

Melanoma of the skin is the most dangerous skin cancer in the world, though the numbers of reported new cases and melanoma-related deaths are low. This study evaluated the global incidence, mortality, risk factors and temporal trends by age, sex and locations of melanoma skin cancer. Cancer Incidence in Five Continents (CI5) volumes I–XI; the Nordic Cancer Registries (NORDCAN); the Surveillance, Epidemiology and End Results (SEER) Program; and the World Health Organization (WHO) International Agency for Research on Cancer (IARC) mortality database were accessed for worldwide incidence and mortality rates. Average Annual Percentage Change (AAPC) was calculated using a Joinpoint regression to examine trends. Age-standardized rates of cancer incidence and mortality were 3.4 and 0.55 per 100,000 worldwide in 2020. Australia and New Zealand reported the highest incidence and mortality rates. Associated risk factors included higher prevalence of smoking, alcohol consumption, unhealthy diet, obesity and metabolic diseases. Increasing incidence trends were observed mostly in European countries, whilst mortality displayed an overall decreasing trend. For both sexes in the age group 50 years and above, a significant increase in incidence trend was observed. Although mortality rates and trends were found to decrease, global incidence has increased, especially in older age groups and males. Whilst incidence increase may be attributed to improved healthcare infrastructure and cancer detection methods, the growing prevalence of lifestyle and metabolic risk factors in developed countries should not be discounted. Future research should explore underlying variables behind epidemiological trends.

Blue nail discoloration is a distinctive clinical presentation, and diagnosis is challenging given the broad differential diagnosis. A comprehensive review of the literature describing blue discoloration of one or multiple nails was performed using the PubMed, Embase, Scopus, and Web of Science databases. A total of 245 publications were included and grouped based on involvement of a single nail (monodactylic) or multiple nails (polydactylic). Monodactylic blue discoloration was associated with tumors or benign nevi, most commonly glomus tumors, followed by blue nevi and less commonly melanomas. Polydactylic blue discoloration was frequently associated with medications (such as minocycline, zidovudine, and hydroxyurea), toxic and exogenous exposures (such as silver), and other medical conditions (such as HIV/AIDS and systemic lupus erythematous). Patients presenting with blue nail discoloration warrant a thorough history, physical examination, and workup to rule out malignancy, systemic disease, or toxic exposure. We present diagnostic algorithms for monodactylic and polydactylic blue nail discoloration to guide workup and treatment plans.

Staphylococcal scalded skin syndrome (SSSS) is a common disorder that is usually seen in infants and children and rarely seen in adults. SSSS usually presents with a prodrome of sore throat or conjunctivitis. Extremely tender flaccid bullae, which are Nikolsky sign-positive, develop within 48 hours and commonly affect the flexures; occasionally, large areas of the skin may be involved. The bullae enlarge and rupture easily to reveal a moist erythematous base, which gives rise to the scalded appearance. SSSS in adults is a rare disorder, though there are now over 50 documented cases. Usually SSSS occurs in predisposed individuals, but not all adults have an underlying illness. Whereas mortality in childhood SSSS is approximately 4%, the mortality rate in adults is reported to be greater than 60%. SSSS is caused by an infection with a particular strain of Staphylococcus aureus, which leads to blistering of the upper layer of the skin, by the release of a circulating exotoxin. It has recently been demonstrated that the exfoliative exotoxin responsible for SSSS leads to the cleavage of desmoglein 1 complex, an important desmosomal protein. The same toxins that are responsible for causing SSSS also cause bullous impetigo. There appears to be a relationship between the disease extent, the amount of toxin produced and whether the toxin is released locally or systemically. As a result there is likely to be a spectrum of disease and there are likely to be a number of milder cases of adult SSSS that go undiagnosed. Social improvements and hygiene have led to a dramatic fall in the number of cases of SSSS. Treatment is usually straightforward, when there is no coexistent morbidity and the presentation is mild, but can be demanding if the patient is particularly ill. SSSS is still associated with mortality, particularly when it occurs in adults.