Post-Hyaluronic Acid Filler Reaction Treated With Abrocitinib: A Case Report.

Post-hyaluronic acid filler nodules are uncommon, unpredictable complications that present a challenge to clinical therapy. We report a case of a female in her fifties who developed edema and nodules 6 weeks after hyaluronic acid (HA) filler injection. After minimal improvement with oral steroids and intralesional hyaluronidase, a trial of oral abrocitinib was initiated, which yielded significant clinical improvement. Thus, abrocitinib may be a novel therapeutic option for delayed-onset nodules following injection of hyaluronic acid. J Drugs Dermatol. 2024;23(1):1355-1356.   doi:10.36849/JDD.7271.

What's New in Topicals for Atopic Dermatitis?

Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care.

Cutaneous Squamous Cell Carcinoma and Lichen Simplex Chronicus Successfully Treated with Topical Cannabinoid Oil: A Case Report and Summary of Cannabinoids in Dermatology.

Cannabidiol is a member of the cannabinoids, consisting of a diverse class of compounds derived from Cannabis sativa. There are three types of cannabinoids based on origin: endocannabinoids (endogenous), phytocannabinoids (plant-derived), and synthetic cannabinoids (synthesized). The endocannabinoid system plays a key role in skin homeostasis, such as proliferation, differentiation, and inflammatory signaling. A 64-year-old woman with a history of multiple squamous cell carcinomas who presented with skin lesions on her bilateral dorsal hands is reported. Her skin biopsies showed lichen simplex chronicus on her left hand and squamous cell carcinoma on her right hand; both lesions resolved with topical application of 20% cannabidiol. Cutaneous adverse events associated with cannabinoid use and potential therapeutic uses of cannabinoids in inflammatory skin diseases and skin cancer are also summarized.

Atopic dermatitisReview of comorbidities and therapeutics.

Atopic dermatitis (AD) is a very common skin disease associated with substantial burdens on patient health and quality of life. Knowledge regarding the pathogenesis of AD has expanded within recent years, leading to novel and efficacious therapeutic agents. Similarly, our knowledge of the impact of AD on patient's mental and physical health has also expanded. This review summarizes updates on the evolution, comorbidities, and therapeutic options of AD. AD is associated with increased cardiovascular risk, allergic diseases, and adverse mental health outcomes. Topical and systemic therapeutics have drastically altered the landscape of AD therapy in recent years.

Multiple skin neoplasms at one site (MUSK IN A NEST): collision tumor consisting of epidermal (macular seborrheic keratosis) and dermal (lichen amyloidosis) components.

A collision tumor is a neoplastic lesion comprised of two or more tumors consisting of distinct cell populations in the concurrent location. Multiple skin neoplasms at one site (MUSK IN A NEST) is a term recently coined to describe two or more cutaneous benign or malignant tumors occurring at the same anatomic site. In retrospective studies, seborrheic keratosis and cutaneous amyloidosis have both individually been documented as a component of a MUSK IN A NEST. This report describes a 42-year-old woman who presented with a pruritic skin condition on her arms and legs of 13 years' duration. Skin biopsy results showed epidermal hyperplasia with hyperkeratosis, hyperpigmentation of the basal layer with mild acanthosis, and evidence of amyloid deposition in the papillary dermis. Based on the clinical presentation and pathology findings, a concurrent diagnosis of macular seborrheic keratosis and lichen amyloidosis was established. A MUSK IN A NEST consisting of a macular seborrheic keratosis and lichen amyloidosis is likely a more common occurrence than implied by the paucity of published cases of this phenomenon.

Smoker's Mustache Revisited: Upper Lip Hair Yellow Discoloration Associated With Tobacco.

Yellow hair discoloration (xanthotrichia) has been observed in several settings. Indeed, acquired xanthotrichia, in addition to environmental and occupational causes, can be observed secondary to either iatrogenic, topical, or systemic exposure to systemic drugs and certain systemic conditions: most commonly essential fatty acid deficiencies, protein deficiency, or vitamin B12 deficiency. Smoker's mustache refers to the acquired yellow discoloration of previously white hair on the cutaneous upper lip of men. These individuals are typically elderly and have a history of smoking either cigarettes, cigars, or pipes of several years' duration. The asymptomatic dyschromia often originates centrally, affecting the hair overlying the philtrum and expanding laterally. The condition is asymptomatic, and affected individuals are either unaware of the color change or not concerned with their altered appearance. Yellow to brown discoloration of the thumbnails, fingernails, or both (such as nicotine sign and/or harlequin nails) may be an accompanying clinical stigma to the smoker's mustache and a clue to the diagnosis. Management options include smoking cessation or hair removal of the discolored hair, or both; however, patients usually elect to continue smoking, maintain their facial hair, and continue to display their distinctive yellow smoker's mustache.

Sun protection behaviors among people living with HIV.

People living with HIV (PLWH) are at increased risk for both melanoma and nonmelanoma skin cancers, but there is currently no data on sun protection behaviors among PLWH. We created a 28-question paper survey to collect information on patient demographics and sun protection behaviors among PLWH. We found that although 71.6% of respondents reported spending at least 30 minutes to two hours in the sun daily, only 29.7% reported consistent use of sunscreen. In addition, 41.9% rarely or never received sunscreen counseling by their healthcare providers. There is therefore a need for increased training for healthcare providers in sun protection behavior counseling for PLWH.

Tuberculosis-Associated Erythema Nodosum.

Erythema nodosum is panniculitis that is frequently observed in women aged 18 to 34 years. It usually occurs as an idiopathic condition; however, it may be associated with drugs, infections, malignancy, pregnancy, and systemic illnesses. Erythema nodosum presents with the sudden onset of tender, warm, erythematous nodules typically on the ankles, knees, and shins. Although the pathogenesis has not been fully elucidated, evidence supports a delayed type IV hypersensitivity reaction. It is often a clinical diagnosis that does not require a biopsy; appropriate work-up and careful medication history are crucial to identifying an underlying etiology if present. This report describes a woman from Vietnam, a tuberculosis endemic country, who presented with erythema nodosum that was determined to be a sequela of latent tuberculosis. Several studies have demonstrated an association between erythema nodosum and tuberculosis, especially in endemic regions. Summarized data reveals the incidence of tuberculosis-associated erythema nodosum to be six percent; however, when individuals with either secondary erythema nodosum or infection-associated erythema nodosum are evaluated, the incidence of tuberculosis-associated erythema nodosum is 11% or 21%, respectively. Evaluation of erythema nodosum should include a tuberculin or QuantiFERON test, chest roentgenogram, and/or an acid-fast bacilli sputum culture if the diagnosis of tuberculosis is being considered.

Lentiviral Gene Therapy in HSCs Restores Lineage-Specific Foxp3 Expression and Suppresses Autoimmunity in a Mouse Model of IPEX Syndrome.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a devastating autoimmune disease caused by mutations in FoxP3, a transcription factor required for the development and function of regulatory T cells (Treg cells). Allogeneic hematopoietic stem cell transplant (HSCT) can be curative, but suitable donors are often unavailable. Here, we demonstrate a strategy for autologous HSCT and gene therapy utilizing a lentiviral vector (LV) to restore FoxP3 expression under the control of endogenous human FOXP3 regulatory elements. Both murine transplant models and humanized mice engrafted with LV-modified HSCs show high levels of LV expression selective for CD4+CD25+FoxP3+ Treg cells. LV transduction of scurfy (FoxP3mut) HSCs restores development of functional FoxP3+ Treg cells that suppress T cell proliferation in vitro and rescue the scurfy autoimmune phenotype in vivo. These findings demonstrate preclinical efficacy for the treatment of IPEX patients by autologous HSC transplant and may provide valuable insights into new cell therapies for autoimmunity.

Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells.

Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 108 to 1 × 109 CD34+ cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34+ cells uses LV inefficiently, because the majority of CD34+ cells are short-term progenitors with a limited post-transplant lifespan. Here, we utilized a clinically relevant, immunomagnetic bead (IB)-based method to purify CD34+CD38- cells from human bone marrow (BM) and mobilized peripheral blood (mPB). IB purification of CD34+CD38- cells enriched severe combined immune deficiency (SCID) repopulating cell (SRC) frequency an additional 12-fold beyond standard CD34+ purification and did not affect gene marking of long-term HSCs. Transplant of purified CD34+CD38- cells led to delayed myeloid reconstitution, which could be rescued by the addition of non-transduced CD38+ cells. Importantly, LV modification and transplantation of IB-purified CD34+CD38- cells/non-modified CD38+ cells into immune-deficient mice achieved long-term gene-marked engraftment comparable with modification of bulk CD34+ cells, while utilizing ∼7-fold less LV. Thus, we demonstrate a translatable method to improve the clinical and commercial viability of gene therapy for genetic blood cell diseases.