Atopic Dermatitis: Pathophysiology.

The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell-mediated immune responses, IgE-mediated hypersensitivity, and environmental factors. Loss-of-function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified, which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell-mediated immune responses and can promote IgE-mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis, which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis.

Adnexal iceberg: pruritic papule on top of a nodule on the back.

Basal cell carcinoma (BCC), one of the most common malignancies, is rarely associated with follicular and apocrine differentiation patterns. This case presents a case of BCC with atypical gross presentation and features of aberrant differentiation. Clinicians should maintain a high level of clinical suspicion for BCC in atypical lesions. Click here for the corresponding questions to this CME article.

Postauricular apocrine hidrocystoma: a case and dermoscopy review.

Apocrine hidrocystoma (AH) is a benign cystic proliferation of apocrine sweat glands that classically presents as a slow-growing nodule on the face, especially in the periorbital region. Histopathological evaluation is required to definitively diagnose an apocrine hidrocystoma. Previous studies have described apocrine hidrocystomas in unusual locations. However, the authors have identified only two reported cases of apocrine hidrocystoma in the postauricular region. We present a third case of a postauricular hidrocystoma in a 26-year-old woman, as well as a brief review of the dermoscopic findings of apocrine hidrocystomas in the existing literature.

A case of resistant pityriasis ribra pilaris responsive to combination acitrentin and ustekinumab.

Pityriasis rubra pilaris is a rare psoriasiform dermatitis. Treatment has been adopted from psoriasis protocols, with topical corticosteroids and systemic retinoids as first-line agents, followed by escalation to biologics for recalcitrant disease. We report a patient with resistant pityriasis rubra pilaris who dramatically improved with acitretin and ustekinumab, a combination not well documented in the literature. The purpose of this letter is to emphasize the potential benefit of dual therapy in patients who fail traditional pityriasis rubra pilaris treatment regimens.

SOX-10 staining in dermal scars.

BACKGROUND: Positive staining for SOX10 and the S100 protein are often used in the evaluation of challenging melanocytic neoplasms including melanoma in patient samples. SOX-10 positivity of non-melanocytes in re-excision specimen could complicate the evaluation of invasive melanoma with an invasive desmoplastic component. Therefore, quantifiable data regarding the positivity of SOX-10 in scars will help dermatopathologists to better identify false positive staining. METHODS: A retrospective analysis was performed on 50 re-excision specimens from 2013 to 2017, with a diagnosis of squamous cell carcinoma (SCC) or squamous cell carcinoma in situ (SCCIS). Blocks of re-excision specimens containing scars were stained for SOX-10; results were evaluated by a board-certified dermatopathologist. The sum of the five highest numbers of high-power field (HPF) counts as a proxy for "SOX-10 stain factor," and cell morphological features were analyzed. MART-1 and CD68 immunohistochemical staining was performed to study possible lineage of these SOX-10 positive cells. RESULTS: All 50 specimens showed varying degrees of SOX-10 positivity for histiocytes. SOX-10 positive histiocytes were present in 86% of re-excision scar tissues, of which 71.3% had spindle-shaped or angulated nuclei, and 61.8% had nuclear sizes larger than typical lymphocytes (7 µm). Within the same area of scars, CD68 staining was floridly positive, where as MART-1 staining was overwhelmingly negative. CONCLUSIONS: This study illustrates a potential diagnostic pitfall of using SOX-10 to evaluate re-excision specimens of melanocytic neoplasms and also suggests a previously undescribed staining pattern in scars of SOX-10 positive cells that are not melanocytes. We postulate that such SOX-10 positive cells may represent a small fraction of histiocytes routinely found in scar tissue.

Botulinum Toxin in the Long-Term Treatment of Refractory Raynaud's Phenomenon

Raynaud's phenomenon is an exaggerated physiological response of blood vessels in the distal extremities to emotional stress and cold. It can be idiopathic or secondary to a connective tissue disorder, such as scleroderma or systemic lupus erythematosus. Treatment for Raynaud's phenomenon consists primarily of lifestyle modifications; if unsuccessful, pharmacotherapy with dihydropyridine calcium channel blockers can be added. Botulinum toxin (BTX-A) is a neurotoxic protein produced by Clostridium botulinum spores. While most widely known for its cosmetic use, BTX-A has many therapeutic utilities due to its ability to inhibit multiple neurotransmitters. In this report, we present a patient with Raynaud's phenomenon refractory to standard therapies whose symptoms resolved after treatment with BTX-A. Follow-up with the patient after one and five years showed no relapse or recurrence of symptoms. J Drugs Dermatol. 2019;18(9):943-945.

Classic features of primary systemic amyloidosis (AL amyloidosis) leading to diagnosis of plasma cell myeloma.

The diagnosis of primary systemic amyloidosis, also known as AL (amyloid light-chain) amyloidosis, is often delayed owing to its nonspecific manifestations as well as its rarity. A 64-year-old woman presented with an eight-month history of significant weight loss, anemia, fatigue, and progressive painful cutaneous lesions on her hands, lips, back, perianal, and vulvar area that were originally treated unsuccessfully with antimalarials and systemic corticosteroids. Histopathological examination revealed an amorphous dermis with pale pink material that demonstrated positive birefringence with Congo red staining. Subsequently, the patient underwent a bone marrow biopsy, which uncovered a plasma cell myeloma, the source of her amyloidogenic protein production.

Darier disease with disseminated herpes simplex virus type 2 infection.

Darier disease (DD), also known as keratosis follicularis or Darier-White disease, is a rare autosomal dominant genodermatosis that presents as hyperkeratotic, warty papules affecting the seborrheic and intertriginous areas. Patients with DD are at risk of secondary infections including the rare complication of Kaposi varicelliform eruption (KVE), a widespread viral infection most commonly caused by herpes simplex virus (HSV). Darier disease with secondary KVE can lead to widespread systemic infection and death. This case report discusses an individual with DD who subsequently developed KVE due to disseminated HSV type 2 infection.

Atopic Dermatitis: Pathophysiology.

The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors. Loss of function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell mediated immune responses and can promote IgE mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis.

A Bullous Flare of a Hyperkeratotic Affair: A Case Report.

BACKGROUND: Darier's disease is an autosomal dominant genodermatosis typified by hyperkeratotic papules and plaques in a predominately seborrheic distribution. The vesiculo-bullous variant of Darier's disease is rare. Several previously reported cases have demonstrated clinical and microscopic features resembling familial benign chronic pemphigus or Hailey-Hailey disease. OBJECTIVES: The objective of this report is to describe an uncommon presentation of Darier's disease, which has been infrequently described in the literature. METHODS: The authors present a case of bullous flare of long-standing Darier's disease. CONCLUSIONS: Darier's disease may assume several atypical morphologies, including vesiculo-bullous lesions.

Squamous Cell Carcinoma In Situ Overlying Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neoplasm that has exhibited an exponential increase in incidence in the past 3 decades. Combined MCC and cutaneous squamous cell carcinoma (SCC/MCC) is an uncommon variant of MCC that exhibits worse prognosis than pure MCC. OBJECTIVE: To describe the clinical presentation, dermoscopy, and histology of an unusual subtype of combined SCC/MCC. METHODS AND RESULTS: A 73-year-old white woman presented with an ulcerated and violaceous 10-mm plaque on her right jawline that had been present for 2 to 3 months. On dermoscopy, the lesion was predominantly milky pink to red with peripheral crusting and large-caliber polymorphous vessels. Histology revealed SCC in situ above and adjacent to MCC. The tumor was excised with clear margins, and sentinel lymph node scintography was negative for nodal involvement.

Cavernous hemangioma-like Kaposi sarcoma: a unique histopathologic variant.

Kaposi sarcoma (KS) is an angiolymphatic neoplasm with multifactorial etiology. Clinically, KS has been divided into 4 distinct types and 3 well-defined histologic stages. Rare reports in the literature have characterized additional unique histopathologic variants. The authors report a case of KS, confirmed with human herpesvirus type 8 and D2-40 staining, which resembled a cavernous hemangioma on histopathology.

Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Preceding Toxic Epidermal Necrolysis Secondary to Sildenafil: A Case Report.

Drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome and Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) are reactive entities of aberrant cytotoxic immunologic reactions to exogenous medications. While they are conventionally seen as distinct, separate conditions, we present a case of a rare evolution of DRESS syndrome into SJS-TEN in the setting of simultaneous amoxicillin-clavulanate initiation and long-term sildenafil use in a 66-year-old South Asian female with a known history of prior DRESS syndrome and pulmonary arterial hypertension. We discuss the conditions leading to her unique clinical presentation and provide considerations for future clinical encounters.