Obstacles to Early Diagnosis and Treatment of Hidradenitis Suppurativa: Current Perspectives on Improving Clinical Management.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can progress to significant tunnels and scars that affect quality of life, especially if diagnosis and treatment are delayed. Average delay after initial presentation of HS symptoms can range from 3 to 10 years in adults and 1 to 2 years in children. Factors associated with diagnostic delay include female gender, non-white race, and greater disease severity at diagnosis. Contributing factors include misdiagnoses, difficulty accessing a dermatologist, hesitation in seeking care due to the stigmatizing nature of the disease, and lack of awareness among providers and patients. While efforts to increase awareness include academic talks at conferences and by foundations geared toward HS, social media offers the opportunity to reach young audiences. Many patients report dissatisfaction with their HS treatments. Better understanding of HS pathophysiology and implementation of clinically focused phenotypes and endotypes can lead to development of more targeted and efficacious therapies. FDA approval of medications for HS beyond adalimumab will increase access to a wider selection of therapies, and implementation of therapeutic drug monitoring may maximize the use of biologics for HS.

Hidradenitis Suppurativa in Pediatric Patients.

Hidradenitis suppurativa is a chronic inflammatory skin disorder primarily affecting apocrine gland-bearing areas, including the axillae, groin, and buttocks. It is reported in up to 2% of Western populations and with increasing incidence in children and adults. Nearly one-third of hidradenitis suppurativa cases occur in pediatric patients and nearly half of patients endorse initial symptoms in childhood. To date, there are few clinical studies and guidelines for pediatric hidradenitis suppurativa. Here, we review the epidemiology, clinical presentation, comorbidities, and management of pediatric hidradenitis suppurativa. We discuss barriers contributing to delays in diagnosis and the significant physical and emotional impact of the disease on children and adolescents.

Advances in biologic and small molecule therapies for hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by painful nodules, abscesses, fistulae, and scarring with a predilection for flexural regions. Several biologics and small molecule inhibitors are being evaluated in clinical trials for treatment. AREAS COVERED: The authors discuss the data available from clinical trials and smaller, high-quality studies for existing and emerging biologic and small molecule inhibitor therapies for treatment of HS. Biologics discussed include TNFα, IL-17, IL-23, IL-12/23, and IL-1 inhibitors. Small molecule inhibitors discussed include PDE4, JAK, TYK, IFX-1, and complement cascade inhibitors. Pharmacokinetics and pharmacodynamics for these drugs are also described. EXPERT OPINION: Trial data and our own experience have shown that about half of HS patients experience improvement with adalimumab. However, there is a significant need for pharmacotherapies with higher efficacy goals as in those used for psoriasis. Many biologics and small molecule inhibitors are being tested in clinical trials. The landscape of upcoming therapies for hidradenitis suppurativa appears promising.

Review of Lasers and Energy-Based Devices for Skin Rejuvenation and Scar Treatment With Histologic Correlations.

BACKGROUND: Lasers and energy-based devices (EBD) are popular treatments for skin rejuvenation and resurfacing. Achieving desired outcomes and avoiding complications require understanding the effects of these devices at a histologic level. Currently, no comprehensive review summarizing the histologic effects of laser and energy-based treatments exists. OBJECTIVE: To describe how lasers and EBD alter skin histology and improve the overall understanding of these devices. MATERIALS AND METHODS: A PubMed search was conducted for studies with histologic analysis of fractional picosecond laser, fractional radiofrequency microneedling, nonablative lasers, and ablative lasers. RESULTS: Fractional picosecond lasers induce intraepidermal and/or dermal vacuoles from laser-induced optical breakdown. Fractional radiofrequency microneedling delivers thermal energy to the dermis while sparing the epidermis, making it safer for patients with darker skin phototypes. Fractional nonablative lasers induce conical zones of coagulation of the epidermis and upper dermis. Ablative lasers vaporize the stratum corneum down to the dermis. Traditional ablative lasers cause diffuse vaporization while fractional ablative lasers generate columns of tissue ablation. CONCLUSION: Lasers and EBD are effective for skin resurfacing and rejuvenation and have different mechanisms with disparate targets in the skin. Safe and effective use of devices requires understanding the histologic laser-tissue interaction.

Systemic comorbidities of rosacea: practice gaps among dermatologists.

Rosacea is a chronic inflammatory skin condition that is associated with multiple systemic comorbidities, with the strongest evidence linking rosacea to hypertension, dyslipidemia, inflammatory bowel disease, and anxiety and depression. To assess dermatologists' awareness of and screening practices for rosacea comorbidities, we developed a survey that was distributed to attendings and residents across four academic dermatology departments in Massachusetts. A total of 73 dermatologists with varying experience participated in the study. Findings demonstrated significant knowledge and practice gaps among academic dermatologists in managing systemic comorbidities in rosacea. In addition, dermatologists' awareness of rosacea comorbidities was negatively correlated with number of years out of residency training, highlighting the need to address this knowledge gap through increased continuing medical education. Importantly, we observed a low screening frequency despite a high awareness of the association between rosacea and ocular comorbidities, suggesting that additional financial, institutional, or practice barriers likely contribute to the low screening rate.

Diet-induced obesity promotes infection by impairment of the innate antimicrobial defense function of dermal adipocyte progenitors.

Infections are a major complication of obesity, but the mechanisms responsible for impaired defense against microbes are not well understood. Here, we found that adipocyte progenitors were lost from the dermis during diet-induced obesity (DIO) in humans and mice. The loss of adipogenic fibroblasts from mice resulted in less antimicrobial peptide production and greatly increased susceptibility to Staphylococcus aureus infection. The decrease in adipocyte progenitors in DIO mice was explained by expression of transforming growth factor-ß (TGFß) by mature adipocytes that then inhibited adipocyte progenitors and the production of cathelicidin in vitro. Administration of a TGFß receptor inhibitor or a peroxisome proliferator-activated receptor-γ agonist reversed this inhibition in both cultured adipocyte progenitors and in mice and subsequently restored the capacity of obese mice to defend against S. aureus skin infection. Together, these results explain how obesity promotes dysfunction of the antimicrobial function of reactive dermal adipogenesis and identifies potential therapeutic targets to manage skin infection associated with obesity.

Dermal White Adipose Tissue: A Newly Recognized Layer of Skin Innate Defense.

Dermal white adipose tissue is a unique layer of adipocytes within the reticular dermis of the skin. Recently, several nonmetabolic activities have been discovered for dWAT and its fibroblast precursors. These functions include antimicrobial defense and roles in hair cycling, wound healing, and thermogenesis. In this review, we discuss recent progress in understanding the role of dermal white adipose tissue in immunity, both as an innate antimicrobial cell type and as an indirect communicator with other cutaneous immunocytes to enhance defense and potentially contribute to inflammatory disease.

Pleomorphic dermal sarcoma in a man with HIV: report with next-generation sequencing analysis and review of the atypical fibroxanthoma/pleomorphic dermal sarcoma spectrum.

Atypical fibroxanthoma (AFX) is a rare cutaneous fibrohistiocytic tumor that typically arises on chronically sun-damaged skin, such as the head and neck, as a nondescript ulcerated papule, nodule, or tumor. The clinical prognosis is usually favorable and metastasis is rare. Pleomorphic dermal sarcoma (PDS), or undifferentiated pleomorphic sarcoma, is a recently introduced diagnostic moniker for AFX-like tumors with more aggressive clinical and histologic features such as necrosis and vascular invasion. The exact relationship between AFX and PDS has been debated. Diagnosis of these tumors is generally based on immunohistochemical staining to exclude other mimics. A wholly specific marker for this tumor does not exist, leading to diagnostic ambiguity in certain cases. Herein, we present a case of pleomorphic dermal sarcoma in a 53-year-old man with human immunodeficiency virus that displayed patchy S100 staining concerning for melanoma upon hospital pathology review. Next-generation sequencing analysis confirmed a mutation pattern consistent with published molecular signatures of AFX/PDS. In discussing this case, we review the current understanding of AFX/PDS and discuss diagnostic pitfalls, as well as emphasize on how next-generation sequencing techniques might improve accuracy in the diagnosis of tumors in the spectrum of AFX/PDS.

Basal Cell Carcinoma with Osteoma Cutis.

Osteoma cutis is the formation of bone within the skin. It can present as either primary osteoma cutis or secondary osteoma cutis. Secondary osteoma cutis is more common and is associated with inflammatory, infectious, and neoplastic disorders, including basal cell carcinoma. A 79-year-old Caucasian man without underlying kidney disease or calcium abnormalities presented with a basal cell carcinoma with osteoma cutis on the chin. Basal cell carcinoma with osteoma cutis has seldom been described; however, the occurrence of this phenomenon may be more common than suggested by the currently published literature. The preferred treatment is surgical excision-with or without using Mohs micrographic technique. When the histopathologic examination reveals bone formation in the skin, clinicians should consider the possible presence of an adjacent malignancy, such as a basal cell carcinoma.

Cutaneous Leukocytoclastic Vasculitis Following Influenza Vaccination in Older Adults: Report of Bullous Purpura in an Octogenarian after Influenza Vaccine Administration.

The influenza vaccination is recommended annually for protection against influenza infection. Adults over 65 years of age are especially vulnerable to complications from influenza infection; in addition, they constitute the largest group of influenza vaccination recipients each year. Cutaneous leukocytoclastic vasculitis involves inflammation of small vessel walls by neutrophils. An 88-year-old man with a history of idiopathic pulmonary fibrosis who developed bullous cutaneous leukocytoclastic vasculitis 14 days after receiving the influenza vaccine is described and the characteristics of influenza-associated cutaneous leukocytoclastic vasculitis in older individuals are reviewed.

The ginseng pimple: an inflammatory papule following ginseng consumption.

Ginseng is a popular herbal remedy derived from the plant roots of the Panax genus and has been used in traditional Asian medicine for thousands of years. In the United States, it has become increasingly popular and is taken for many conditions, including as an immune enhancer. Cutaneous adverse effects have been reported to occur following ginseng consumption, although detailed clinical descriptions are limited. A 60-year-old woman who repeatedly developed inflammatory papules following ginseng consumption is described and the characteristics of ginseng use in healthcare are reviewed.

Parrot Beak Nails Revisited: Case Series and Comprehensive Review.

The term "parrot beak nail" describes a morphologic change of the nail plate characterized by excessive forward curvature. It may be associated with systemic disease or, most commonly, occurs as an idiopathic finding complicated by delayed nail plate trimming. The characteristics of parrot beak nails in ten men are described, and the features of this acquired nail deformity are reviewed. Of the ten patients, six presented with concurrent neuropathies that resulted in frequent foot injuries or falls. While the true incidence of parrot beak nails is unknown, this nail deformity occurred in 2.1 % of patients seen by a single physician during a 3-month period. In conclusion, parrot beak nails secondary to poor nail care may lead to functional impairment, tissue injury, and subsequent infections. Therefore, it is important for clinicians to look for these nail lesions on cutaneous examination and recommend frequent nail trimmings to individuals with parrot beak nails.

Edema Bullae Mimicking Disseminated Herpes Zoster.

Edema bullae typically forms at the site of skin swelling during acute states of volume overload, most commonly during renal or cardiac failure. Herpes zoster is a reactivation of latent varicella zoster virus that typically presents as painful vesicles in a dermatomal distribution. In immunocompromised individuals, disseminated herpes zoster skin manifestations may occur with several lesions in multiple dermatomes or widespread individual lesions or both, even visceral organs can be involved. Additionally, many conditions are known to mimic the lesions and distribution of herpes zoster. A 53-year-old immunosuppressed male with a history of renal transplant presented with dermatomal and non-dermatomal, disseminated herpes zoster that was confirmed by polymerase chain reaction testing. After one week of intravenous antiviral therapy during which his virus infection-associated lesions were resolved, new blisters developed near the insertion site of a peripheral venous line located on a previously uninvolved yet swollen upper extremity. The varicella zoster virus disease was initially suspected, but lab studies and skin biopsy of a blister excluded progressive or persistent viral infection and established a diagnosis of acute edema bullae. The blisters resolved following removal of the peripheral catheter. Acute edema bullae should be added to the list of mimickers of disseminated varicella zoster virus infection.

Erythrodermic Psoriasis in a Man with Monoclonal B-cell Lymphocytosis.

Erythroderma is characterized by erythema involving greater than 90% of the body surface area and may be caused by several etiologies, including erythrodermic psoriasis. Psoriasis is an autoimmune skin and systemic condition characterized by erythematous and scaly plaques. Monoclonal B-cell lymphocytosis is an asymptomatic hematological disorder diagnosed by elevated, small, clonal B-cell counts in the peripheral blood. The characteristics of a 71-year-old man with new onset of erythrodermic psoriasis and concurrent monoclonal B-cell lymphocytosis are presented. The simultaneous development of these two conditions raises the possibility that they may share a related pathogenesis.

Hydrogen sulfide suppresses oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 generation from macrophages via the nuclear factor κB (NF-κB) pathway.

This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine-ß-synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-κB and ox-LDL-induced NF-κB activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-κB p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-κB pathway activation in ox-LDL-induced macrophage inflammation.