Disseminated Histoplasmosis Diagnosed by "Touch Prep".

Disseminated histoplasmosis is a rare but serious complication of infection with the dimorphic fungus Histoplasma capsulatum. We report a case of disseminated histoplasmosis with cutaneous involvement diagnosed by touch wet preparation and confirmed with histopathology and culture. "Touch prep" performed from a lesional punch biopsy, prepared with Wright-Giemsa followed by chlorazol black containing KOH, revealed abundant yeast organisms localized within multinucleated giant cells, and a rapid diagnosis of disseminated histoplasmosis with cutaneous involvement was achieved. This report demonstrates the utility of wet prep techniques as an invaluable and rapid beside diagnostic tool in the setting of cutaneous histoplasmosis. In addition, we compare the distinguishing histopathologic features of the infectious organisms within the differential diagnosis of parasitized histiocytes.

Uveitis for Dermatologists: A Review.

Certain dermatologic conditions and drugs used for their treatment are associated with uveitis, a vision-threatening group of inflammatory eye diseases. Dermatologists may therefore be the first healthcare providers to recognize the presence of uveitis in certain patients and can help ensure morbidity is minimized. Posterior uveitis in particular, which may manifest as insidious, painless vision loss, may first be identified by a careful review of systems by a dermatologist. Understanding uveitis and its associations with certain skin findings and drugs will help enable identification and triage of patients in need of ophthalmic care. An overview of uveitis is provided, including its epidemiology, etiologies, classification, presenting signs and symptoms, general management, and complications. Next, dermatologic diseases that may be associated with uveitis are reviewed with a focus on how uveitis is most likely to present. Lastly, drugs used by dermatologists and less common dermatologic diseases associated with uveitis are reviewed. Multidisciplinary management is necessary for patients with both skin disease and ocular complications such as uveitis. Dermatologists’ recognition of uveitis in patients may reduce time to referral and improve patient outcomes. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5165.

Herpes zoster at the vaccination site in immunized healthy children.

In this case series, we report seven immunized healthy children without underlying immunodeficiency who presented with herpes zoster that correlated with varicella-zoster vaccination site. The morphology of the lesions included erythematous papules, pseudovesicles, and plaques, with associated pain in two and pruritus in three patients; systemic symptoms ranged from none to low-grade fevers, upper respiratory symptoms, and joint pain. These cases highlight the clinical, diagnostic, and therapeutic implications of herpes zoster in vaccinated children.

Vitamin D receptor and CD86 expression in the skin of vitamin D-deficient swine.

The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-κB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D-sufficient swine. There was no difference in the immunostaining for NF-κB. Since VDR and CD86 expression are decreased in the setting of melanoma and non-melanoma skin cancers, our findings suggest a potential role of vitamin D-deficiency in the progression of skin malignancies.

Dermatologic side effects of psychotropic medications.

BACKGROUND: Although relatively uncommon, cutaneous reactions to psychotropic medications may thwart treatment of psychiatric illness and confuse diagnostic efforts especially when they occur in the context of comorbid medical conditions. Psychiatrists may be asked to comment on whether a particular cutaneous condition is due to a psychotropic medication or to recommend a replacement psychotropic agent. OBJECTIVE: To review the available literature describing cutaneous adverse effects prompted by psychotropic medications. METHOD: A search of the literature using PubMed was undertaken using the terms "psychotropic," "psychiatric," "antidepressant," "anxiolytic," "mood stabilizer," "antipsychotic," and "neuroleptic" in combination with either of the terms "dermatologic," "cutaneous" or "skin." RESULTS: Psychotropic medications from all classes have been associated with a broad variety of dermatologic reactions with variable rates of incidence. Psychiatrists should be aware of the potential cutaneous adverse effects of the medications they prescribe. Psychiatrists practicing in the general hospital, where cutaneous symptoms may present for any number of reasons, should be aware of the typical presentations and relative likelihood of these reactions to forestall unnecessary "blaming" of psychotropics for cutaneous reactions.

Epigenetics in the pathogenesis and pathophysiology of psoriasis vulgaris.

Epigenetic phenomena, including DNA methylation, histone modification, and genetic regulation by miRNAs, are potentially heritable genetic regulatory changes that are not attributed to direct alterations in the DNA sequence of base pairs. They may explain the link between psoriasis risk alleles and disease development, as alleles possess various potentials to undergo epigenetic modification. Multiple genes involved in psoriasis pathogenesis demonstrate abnormal methylation patterns including those involved in epidermal differentiation and proliferation, immunity, the cell cycle, apoptosis, inflammation, and IFN-γ and TNF-α signaling. Hypoacetylation of histone H4 is observed in peripheral blood mononuclear cells of psoriatic patients, and the degree of hypoacetylation of histone H4 is inversely correlated to the PASI score. Investigators have reported both increased and decreased expression of miRNAs in patients with psoriasis, and have described and speculated a number of possible mechanisms for their roles in pathogenesis. Interestingly, the altered methylation patterns observed in psoriasis appear to be normalized by treatment with biologics directed at TNF-α inhibition. However, attempts to directly correlate epigenetic regulatory mechanisms with expression of genes observed in psoriasis have been limited thus far, and correlating miRNA expression levels to disease phenotypes can be challenging and inconsistent. Hopefully, the goal of drawing clinically relevant conclusions about the role of epigenetics in psoriasis will be aided by recent methods that enable fast and sensitive epigenomic profiling. Drugs targeting epigenetic mechanisms are currently being explored, though not for psoriasis, but specificity to pathogenetic mechanisms remains elusive. However, the amenability of cutaneous disease to topical therapies may elevate their usefulness in the treatment of this common skin disorder.

What's Eating You? Culex Mosquitoes and West Nile Virus.

West Nile virus (WNV) commonly presents cutaneously as a maculopapular rash on the trunk and extremities that most often appears around the time of defervescence and may serve as a positive prognostic indicator. Several laboratory tests can aid in diagnosis of WNV, including an IgM enzyme-linked immunosorbent assay (ELISA), but an antibody response may not be detectable for up to 8 days after symptom onset. Taking a comprehensive history in any patient presenting with a generalized maculopapular rash, fever, nonspecific symptoms, or neurologic changes can aid the astute dermatologist in promptly recognizing the possibility of WNV.

Clinical, Dermatoscopic, and Histological Findings in a Diagnosis of Pityriasis Lichenoides.

Pityriasis lichenoides et varioliformis acuta (PLEVA) is a rare cutaneous eruption of erythematous macules and papules distributed over the flexural surfaces and the trunk. Histopathologic analysis is useful in diagnosis, and dermoscopic findings have been described in several small case series. We present a case of a mid-20s female who was diagnosed with PLEVA based on clinical and histopathological findings, and we also demonstrate a unique dermoscopic finding. Additionally, we review the current literature detailing dermoscopy findings with associated histopathology in PLEVA and pityriasis lichenoides chronica (PLC).

Trachyonychia Secondary to Acitretin Usage.

Trachyonychia is a disease of the nail matrix that most commonly presents with sandpaper-like roughness of the nails. Retinoids are known to cause several nail abnormalities, likely due to their anti-proliferative effects. Despite this, no cases have been previously reported on the association of acitretin (second-generation retinoid) with trachyonychia. We present a single case of trachyonychia associated with acitretin that subsided following medication cessation.

Kaposi's varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab.

BACKGROUND: Immune-directed therapies have become front-line therapy for melanoma and are transforming the management of advanced disease. In refractory cases, multi-modal immunoncology (IO) approaches are being utilized, including combining immune checkpoint blockade (ICB) with oncolytic herpes viruses. Talimogene laherparepvec (T-VEC) is the first genetically modified oncolytic viral therapy (OVT) approved for the treatment of recurrent and unresectable melanoma. The use of IO in patients with concomitant malignancies and/or compromised immune systems is limited due to systematic exclusion from clinical trials. For example, a single case report of a solid organ transplant patient successfully treated with T-VEC for metastatic melanoma has been reported. Furthermore, the use of ICB in T-cell malignancies is limited and paradoxical worsening has been described. To our knowledge, this is the first report of dual ICB/T-VEC being administered to a patient with concurrent primary cutaneous anaplastic large cell lymphoma (pcALCL) and melanoma. CASE PRESENTATION: Here we present the case of a patient with concomitant primary cutaneous ALCL and metastatic melanoma, progressing on anti-programmed death (PD)-1 therapy, who developed Kaposi's varicelliform eruption after receiving the first dose of Talimogene laherparepvec. CONCLUSION: This case highlights the complexities of care of patients with coexistent cancers, demonstrates rapid progression of primary cutaneous ALCL on nivolumab and introduces a novel adverse effect of Talimogene laherparepvec.

High-mobility Group Box Protein-1, Matrix Metalloproteinases, and Vitamin D in Keloids and Hypertrophic Scars.

Keloids and hypertrophic scars represent excessive wound healing involving high production of collagen by skin fibroblasts. This review focuses on the role of high-mobility group box protein-1 (HMGB-1), matrix metalloproteinases (MMPs), and vitamin D in these conditions. Although the role of HMGB-1 in keloids and hypertrophic scars is unclear, the effect of HMGB-1 on fibroblasts suggests a profibrotic role and a potential contribution to excessive scarring. MMPs contribute extensively to wound healing and characteristically degrade the extracellular matrix. MMP-1 is decreased in keloids and hypertrophic scars. However, other MMPs, including MMP-2, have been found to be increased and are thought to possibly contribute to keloid expansion through peripheral extracellular matrix catabolism. Many novel therapeutic approaches to keloids and hypertrophic scars target MMPs and aim to increase their levels and catabolic activity. The higher prevalence of keloids in darker skin types may partially be due to a tendency for lower vitamin D levels. The physiologically active form of vitamin D, 1,25(OH)2D3, inhibits the proliferation of keloid fibroblasts, and correlations between vitamin D receptor polymorphisms, such as the TaqI CC genotype, and keloid formation have been reported. Additionally, vitamin D may exert an antifibrotic effect partially mediated by MMPs. Here, we critically discuss whether keloid and hypertrophic scar formation could be predicted based on vitamin D status and vitamin D receptor polymorphisms. Specifically, the findings identified HMGB-1, MMPs, and vitamin D as potential avenues for further clinical investigation and potentially novel therapeutic approaches to prevent the development of keloids and hypertrophic scars.

Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma.

The tumor microenvironment plays an important role in the progression of melanoma, the prototypical immunologic cutaneous malignancy. The triggering receptor expressed on myeloid cells (TREM) family of innate immune receptors modulates inflammatory and innate immune signaling. It has been investigated in various neoplastic diseases, but not in melanoma. This study examines the expression of TREM-1 (a proinflammatory amplifier) and TREM-2 (an anti-inflammatory modulator and phagocytic promoter) in human cutaneous melanoma and surrounding tissue. Indirect immunofluorescence staining was performed on skin biopsies from 10 melanoma patients and staining intensity was semiquantitatively scored. Expression of TREM-1 and TREM-2 was higher in keratinocytes than melanoma tissue (TREM-1: p < 0.01; TREM-2: p < 0.01). Whereas TREM-2 was the dominant isoform expressed in normal keratinocytes, TREM-1 expression predominated in melanoma tissue (TREM-1 to TREM-2 ratio: keratinocytes = 0.78; melanoma = 2.08; p < 0.01). The increased TREM ratio in melanoma tissue could give rise to a proinflammatory and protumor state of the microenvironment. This evidence may be suggestive of a TREM-1/TREM-2 paradigm in which relative levels dictate inflammatory and immune states, rather than absolute expression of one or the other. Further investigation regarding this paradigm is warranted and could carry prognostic or therapeutic value in treatment for melanoma.

Immunomodulation of malignant melanoma by contact sensitizing agents.

The importance of host defense against malignant melanoma is underlined by the use of immunomodulating agents as effective therapies. Diphencyprone and 2,4-dinitrochlorobenzene (DNCB) have been used successfully as contact sensitizing agents in this regard. Through haptenation of cell surface and cytoplasmic proteins, these agents trigger a CD8(+) T-lymphocyte predominant allergic contact hypersensitivity response. Th17 cells may also play a critical role. The effectiveness of these agents at stimulating tumor defense may be limited to melanoma of the skin. Response to immunotherapy using diphencyprone and DNCB is governed by the immune status of the host, which is affected by tumor burden, UV light and age. Additionally, diphencyprone and DNCB elicit synergy with other methods of treatment and thus may be used as adjuncts. Two current prospective trials may aid in elucidating the impact that this treatment modality has on the prognosis and quality of life of patients with melanoma.