Extramammary Paget Disease. Part II. Evidence-based Approach to Management.

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and non-invasive therapies, as well as novel approaches for advanced disease.

Ustekinumab for the treatment of paradoxical skin reactions and cutaneous manifestations of inflammatory bowel diseases.

Ustekinumab (STELARA), a human monoclonal antibody directed against IL-12 and IL-23, is FDA-approved to treat psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. Increasing recognition of paradoxical skin reactions induced by older biologic therapies used for inflammatory bowel diseases (IBD), such as, adalimumab and infliximab, has led to the investigation of ustekinumab for the treatment of the cutaneous and gastrointestinal manifestations of IBD. In addition, ustekinumab may show efficacy in treating paradoxical cutaneous reactions to tumor necrosis factor-alpha (TNF-α) inhibitors. A search of the Medline/PubMed database, with additional citations obtained from the references section of relevant articles, yielded 22 articles that were included in this review. Ustekinumab is a safe and effective option for treating the cutaneous manifestations of IBD, such as, metastatic Crohn's disease and pyoderma gangrenosum. It is also an effective treatment for TNF-α inhibitor-induced paradoxical skin reactions, such as, psoriasis that do not remit spontaneously or with conventional treatment. Additional studies should focus on the optimal dosing of ustekinumab for dermatologic conditions beyond psoriasis.

Sweet syndrome as an adverse reaction to tyrosine kinase inhibitors: A review.

Tyrosine kinase inhibitors are a class of targeted anticancer drugs that inhibit cancer cell proliferation by inactivating proteins involved in signal transduction cascades. Various cutaneous adverse events have been observed after tyrosine kinase inhibitor administration, including Sweet syndrome. We queried the PubMed database to identify 14 cases of Sweet syndrome thought to be secondary to tyrosine kinase inhibitors. Tyrosine kinase inhibitor-induced Sweet syndrome had a median of 2 months latency following drug administration. All cases but one had morphologic features classic for Sweet syndrome (erythematous and tender papules, plaques, or nodules). All cases also had classic histopathologic findings (dermal neutrophilic infiltrate without vasculitis or necrosis). Using diagnostic criteria for drug-induced Sweet syndrome and the Naranjo Drug Reaction Probability Scale for a drug-induced cutaneous eruption, we found that six cases favored a drug-induced etiology over malignancy, two cases favored a malignancy-associated Sweet syndrome, and the remaining eight met drug-induced Sweet syndrome criteria but had low Naranjo scores. Nine cases resulted in medication discontinuation, while five cases continued anticancer therapy and were treated only with corticosteroids with quick resolution of skin lesions. Dermatologists should be aware of this adverse cutaneous reaction to tyrosine kinase inhibitors and should treat on a case-by-case basis, though limited evidence in this review suggests that oncologic therapy may safely be continued with prompt corticosteroid treatment.

Update on Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a lifetime prevalence of up to 20% which can occur at any age but is most common among children. There is a significant burden of pediatric AD in the primary care setting; thus, the ability to recognize and manage AD is of utmost importance to pediatricians. Treatment of AD requires a multifaceted approach based on a patient's severity including behavioral modifications, topical and systemic pharmacologic therapies, and phototherapy.

Off-label studies on ruxolitinib in dermatology: a review.

Ruxolitinib is a Janus kinase (JAK) inhibitor that is FDA-approved for the treatment of myelofibrosis, polycythemia vera, and acute graft-versus-host disease. Its use in treating various dermatologic diseases has been a topic of growing interest due to its favorable safety profile and targeted inhibition of several cytokines that perpetuate inflammatory skin conditions. The PubMed/MEDLINE and ClinicalTrials.gov databases were searched for literature on off-label uses of ruxolitinib in dermatology and ongoing trials studying its safety and efficacy. There is randomized controlled trial (RCT) evidence for the successful use of ruxolitinib in treating alopecia, atopic dermatitis, and psoriasis, with ongoing RCTs for its use in vitiligo. Smaller studies have confirmed the success of ruxolitinib in treating conditions such as dermatomyositis and hypereosinophilic syndrome, among others. No serious adverse effects were reported with the use of ruxolitinib in dermatology, but further research is needed to determine its efficacy, delivery route, and optimal dosing for treating dermatologic conditions.

Integrating primary palliative care into hidradenitis suppurativa management.

Hidradenitis suppurativa (HS) is a chronic, often debilitating skin condition that disproportionately impacts women in the United States and other Western nations. Dermatologists should consider incorporating palliative care principles into HS management to optimize care. Primary palliative care principles include utilizing evidence-based frameworks in serious illness communication, acknowledging and addressing physical and psychosocial suffering, recognizing and validating the burden of disease in partners, families, and caregivers, and engaging in collaborative care coordination. Certain patients may also benefit from outpatient, or sometimes inpatient, palliative care specialist collaboration, such as those with refractory HS and superimposed challenging psychosocial dynamics and symptom burden. Through integration of these palliative care domains into HS care, dermatologists can optimize their ability to provide comprehensive and compassionate care for patients suffering with this disease.

Clinical pearl: Expanding knowledge of emergency contraception among dermatologists.

Dermatologists prescribe teratogenic or potentially teratogenic medications to treat a variety of skin diseases, including spironolactone for hormonal dysregulation in hidradenitis suppurativa or isotretinoin for severe acne. Although contraceptive options are regularly discussed, dermatologists must also be familiar with emergency contraceptive methods in the case that patients receiving teratogenic medications engage in unprotected sexual intercourse and do not desire pregnancy. A lack of knowledge regarding emergency contraceptive options may represent a practice gap for dermatologists.

Reversible acral and mucosal hyperpigmentation in a patient with B12 deficiency secondary to polyglandular autoimmune syndrome type II.

Reversible cutaneous hyperpigmentation often occurs in the setting of nutritional deficiencies and protein energy malnourishment, with atypical presentations arising from autoimmune disease. Here, we present a 52-year-old female with hypertension, type 1 diabetes, and Hashimoto's thyroiditis, under the diagnosis of polyglandular autoimmune syndrome type II, referred for evaluation of asymptomatic hyperpigmentation of the palms, soles, hard palate, and tongue for 6 months. The patient underwent a significant work-up, including esophagogastroduodenoscopy, which revealed hypertrophic gastropathy as well as evidence of acquired B12 deficiency secondary to pernicious anemia. The patient was initiated on B12 supplementation, with eventual resolution of mucocutaneous findings.

BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities.

The Bone Morphogenetic Protein (BMP) family reiteratively signals to direct disparate cellular fates throughout embryogenesis. In the developing dorsal spinal cord, multiple BMPs are required to specify sensory interneurons (INs). Previous studies suggested that the BMPs act as concentration-dependent morphogens to direct IN identity, analogous to the manner in which sonic hedgehog patterns the ventral spinal cord. However, it remains unresolved how multiple BMPs would cooperate to establish a unified morphogen gradient. Our studies support an alternative model: BMPs have signal-specific activities directing particular IN fates. Using chicken and mouse models, we show that the identity, not concentration, of the BMP ligand directs distinct dorsal identities. Individual BMPs promote progenitor patterning or neuronal differentiation by their activation of different type I BMP receptors and distinct modulations of the cell cycle. Together, this study shows that a 'mix and match' code of BMP signaling results in distinct classes of sensory INs.