The "bumpy" adolescent nose: Acne associated angiofibroma-like nasal papules.

BACKGROUND/OBJECTIVE: Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS: In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS: We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION: We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.

What's New in Dermatopathology: Inflammatory Dermatoses.

Inflammatory skin diseases encompass a vast array of conditions. The field continues to expand and evolve with resurgence of conditions, through newly recognized medication adverse effects, and via more detailed descriptions of known dermatoses. The importance of clinicopathologic correlation and an up to date knowledge of dermatologic conditions cannot be overstated. This review focuses on an array of recent important developments in the histologic diagnosis of inflammatory conditions that affect the skin.

Lichen planus pigmentosus.

Lichen planus pigmentosus (LPP) is an uncommon variant of lichen planus of unclear etiology that predominantly affects patients of skin types III to VI. We report a case of LPP of two years duration in a 67-year-old man involving upper extremities, chest, abdomen, and upper back.

Silicone granulomas with ulcers.

We present a 42-year-old transgender womanwith woody induration over her buttocks andlower extremities as well as persistent ulcers of thebuttocks. The lesions developed ten years prior to herpresentation and approximately five years after shereceived illegal silicone injections to her buttocks.Histopathologic examination was consistent witha silicone granuloma. Silicone granuloma is a notan uncommon side effect of silicone injections andmore often occurs when the filler is administeredby non-physician practitioners, as is the case in thispatient. Ulcerative silicone granulomas, however,rarely are reported. In this case, the patient'shemodialysis treatments, which required longperiods of weight bearing on her buttocks, may havepredisposed her to ulcers in this area, and the ulcersmay have been in part due to poor vascular supplyas well as physical pressure. Treatment of this patientis relatively challenging, owing to her multiplecomorbidities that include end-stage renal diseaseand congestive heart failure.

Generalized granuloma annulare in a folliculocentric distribution.

We present a 69-year-old man with type 2 diabetes mellitus and a five-year history of an eruption of follicular pustules, papules, and nodules, which was identified histopathologically as folliculocentric granuloma annulare (GA). Folliculocentric generalized GA is a rarely reported variant of GA, in which the the palisading histiocytes form focal granulomas in a follicular pattern. In this case, the GA may represent an isotopic phenomenon, with lesions developing in hair follicles that were previously affected by a suppurative folliculitis.

Squamous-cell carcinoma in situ.

We present a 30-year-old woman with atopic dermatitis and ichthyosis vulgaris and a one-year history of an erythematous, scaly plaque on the dorsal surface of her right hand, which developed three years after an accidental exposure to prolonged ultraviolet C (UVC) radiation in a laboratory accident. The plaque, which was initially treated as eczematous dermatitis, was eventually identified histopathologically as squamous-cell carcinoma in situ. Although causation is not definitive, this case is the first to describe development of non-melanoma skin cancer (NMSC) in an area of skin known to be acutely exposed to UVC radiation. As UVC radiation becomes a more frequently used anti-microbial technology, UVC radiation may become a more commonly identified risk factor in the development of NMSC.

Iododerma following serial computed tomography scans in a lung cancer patient.

Iododerma is a rare cutaneous eruption occurring after iodine administration. Nine cases of iododerma following intravenous contrast have been reported in the English-language literature, typically in patients with renal insufficiency. We report a case of iododerma in a patient with relatively unimpaired renal function who underwent serial computer tomography (CT) scans with intravenous contrast. An 81-year-old woman with stage IV lung cancer developed fever and rash following serial CT scans with iodixanol contrast media. On examination, we noted conjunctival injection, enlarged glands, oral ulcers, and erythematous papules and plaques on her forehead, arms, and legs. Random urine iodine was elevated to 106,767 µg/L (normal range, 26-705 µg/L). Skin biopsy revealed diffuse predominantly neutrophilic dermal infiltrate. The patient's clinical presentation, laboratory findings, and biopsy results were consistent with iododerma. Iododerma can occur in patients with adequate kidney function, and its presentation can include ocular and glandular symptoms, as in this case. Withdrawal of the source of iodine typically leads to resolution of symptoms.

Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa.

Revertant mosaicism is a naturally occurring phenomenon involving spontaneous correction of a pathogenic gene mutation in a somatic cell. It has been observed in several genetic diseases, including epidermolysis bullosa (EB), a group of inherited skin disorders characterized by blistering and scarring. Induced pluripotent stem cells (iPSCs), generated from fibroblasts or keratinocytes, have been proposed as a treatment for EB. However, this requires genome editing to correct the mutations, and, in gene therapy, efficiency of targeted gene correction and deleterious genomic modifications are still limitations of translation. We demonstrate the generation of iPSCs from revertant keratinocytes of a junctional EB patient with compound heterozygous COL17A1 mutations. These revertant iPSCs were then differentiated into naturally genetically corrected keratinocytes that expressed type XVII collagen (Col17). Gene expression profiling showed a strong correlation between gene expression in revertant iPSC-derived keratinocytes and the original revertant keratinocytes, indicating the successful differentiation of iPSCs into the keratinocyte lineage. Revertant-iPSC keratinocytes were then used to create in vitro three-dimensional skin equivalents and reconstitute human skin in vivo in mice, both of which expressed Col17 in the basal layer. Therefore, revertant keratinocytes may be a viable source of spontaneously gene-corrected cells for developing iPSC-based therapeutic approaches in EB.

Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.

Alopecia areata (AA) is a common autoimmune disease resulting from damage of the hair follicle by T cells. The immune pathways required for autoreactive T cell activation in AA are not defined limiting clinical development of rational targeted therapies. Genome-wide association studies (GWAS) implicated ligands for the NKG2D receptor (product of the KLRK1 gene) in disease pathogenesis. Here, we show that cytotoxic CD8(+)NKG2D(+) T cells are both necessary and sufficient for the induction of AA in mouse models of disease. Global transcriptional profiling of mouse and human AA skin revealed gene expression signatures indicative of cytotoxic T cell infiltration, an interferon-γ (IFN-γ) response and upregulation of several γ-chain (γc) cytokines known to promote the activation and survival of IFN-γ-producing CD8(+)NKG2D(+) effector T cells. Therapeutically, antibody-mediated blockade of IFN-γ, interleukin-2 (IL-2) or interleukin-15 receptor ß (IL-15Rß) prevented disease development, reducing the accumulation of CD8(+)NKG2D(+) T cells in the skin and the dermal IFN response in a mouse model of AA. Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-γ and γc cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease. Notably, three patients treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near-complete hair regrowth within 5 months of treatment, suggesting the potential clinical utility of JAK inhibition in human AA.

Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle.

Duchenne muscular dystrophy is characterized by progressive muscle weakness and early death resulting from dystrophin deficiency. Loss of dystrophin results in disruption of a large dystrophin glycoprotein complex, leading to pathological calcium (Ca2+)-dependent signals that damage muscle cells. We have identified a structural and functional defect in the ryanodine receptor (RyR1), a sarcoplasmic reticulum Ca2+ release channel, in the mdx mouse model of muscular dystrophy that contributes to altered Ca2+ homeostasis in dystrophic muscles. RyR1 isolated from mdx skeletal muscle showed an age-dependent increase in S-nitrosylation coincident with dystrophic changes in the muscle. RyR1 S-nitrosylation depleted the channel complex of FKBP12 (also known as calstabin-1, for calcium channel stabilizing binding protein), resulting in 'leaky' channels. Preventing calstabin-1 depletion from RyR1 with S107, a compound that binds the RyR1 channel and enhances the binding affinity of calstabin-1 to the nitrosylated channel, inhibited sarcoplasmic reticulum Ca2+ leak, reduced biochemical and histological evidence of muscle damage, improved muscle function and increased exercise performance in mdx mice. On the basis of these findings, we propose that sarcoplasmic reticulum Ca2+ leak via RyR1 due to S-nitrosylation of the channel and calstabin-1 depletion contributes to muscle weakness in muscular dystrophy, and that preventing the RyR1-mediated sarcoplasmic reticulum Ca2+ leak may provide a new therapeutic approach.