Cloyce L. Stetson

Role of the steroidogenic acute regulatory protein in health and disease

Steroid hormones are an important class of regulatory molecules that are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta, brain, and skin, and influence a spectrum of developmental and physiological processes. The steroidogenic acute regulatory protein (STAR) predominantly mediates the rate-limiting step in steroid biosynthesis, i.e., the transport of the substrate of all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane. At the inner membrane, cytochrome P450 cholesterol side chain cleavage enzyme cleaves the cholesterol side chain to form the first steroid, pregnenolone, which is converted by a series of enzymes to various steroid hormones in specific tissues. Both basic and clinical evidence have demonstrated the crucial involvement of the STAR protein in the regulation of steroid biosynthesis. Multiple levels of regulation impinge on STAR action. Recent findings demonstrate that hormone-sensitive lipase, through its action on the hydrolysis of cholesteryl esters, plays an important role in regulating STAR expression and steroidogenesis which involve the liver X receptor pathway. Activation of the latter influences macrophage cholesterol efflux that is a key process in the prevention of atherosclerotic cardiovascular disease. Appropriate regulation of steroid hormones is vital for proper functioning of many important biological activities, which are also paramount for geriatric populations to live longer and healthier. This review summarizes the current level of understanding on tissue-specific and hormone-induced regulation of STAR expression and steroidogenesis, and provides insights into a number of cholesterol and/or steroid coupled physiological and pathophysiological consequences.

Linear Morphea Presenting as Acquired Unilateral Edema

Abstract:  We describe a 2‐year‐old African‐American boy with a 4‐month history of gradually worsening unilateral edema that was initially noted on his left hand and then approximately 2 weeks later on his left lower extremity. In addition, linear hypopigmented patches were noted along the left forearm and leg, with no appreciable scarring or induration. The edema on the left‐hand side of his body progressed so that he developed tense bullae on his left hand. Two months later, the hypopigmented patches were indurated and bound‐down, especially over the left groin and thigh. A biopsy specimen from this area showed features characteristic of morphea. In this patient, dilated lymphatic channels secondary to the sclerosis of the morphea caused the bullae. Bullous morphea is a rare condition. We were unable to find any reports its occurrence in children under 18 with associated lymphedema. This entity should be included in the differential for acquired unilateral edema in children.

Up-regulation of steroid biosynthesis by retinoid signaling: Implications for aging

Retinoids (vitamin A and its derivatives) are critical for a spectrum of developmental and physiological processes, in which steroid hormones also play indispensable roles. The StAR protein predominantly regulates steroid biosynthesis in steroidogenic tissues. We have reported that regulation of retinoid, especially atRA and 9-cis RA, responsive StAR transcription is largely mediated by an LXR-RXR/RAR heterodimeric motif in the mouse StAR promoter. Herein we demonstrate that retinoids are capable of enhancing StAR protein, P-StAR, and steroid production in granulosa, adrenocortical, glial, and epidermal cells. Whereas transient expression of RARα and RXRα enhanced 9-cis RA induced StAR gene transcription, silencing of RXRα with siRNA, decreased StAR and steroid levels. An oligonucleotide probe encompassing an LXR-RXR/RAR motif bound to adrenocortical and epidermal keratinocyte nuclear proteins in EMSAs. ChIP studies revealed association of RARα and RXRα with the StAR proximal promoter. Further studies demonstrated that StAR mRNA levels decreased in diseased and elderly men and women skin tissues and that atRA could restore steroidogenesis in epidermal keratinocytes of aged individuals. These findings provide novel insights into the relevance of retinoid signaling in the up-regulation of steroid biosynthesis in various target tissues, and indicate that retinoid therapy may have important implications in age-related complications and diseases.

Extensive Cutaneous Botryomycosis With Subsequent Development of Nocardia-Positive Wound Cultures:

Botryomycosis is a rare, chronic granulomatous infection caused by a response to bacteria, most commonly Staphylococcus aureus. Cutaneous manifestations, such as subcutaneous nodules, nonhealing ulcers, or sinus tracks, typically occur following inoculation of bacteria after trauma. Drainage from the skin lesions may contain yellow grains resembling those seen in actinomycosis and nocardiosis. A 20-year-old Hispanic male presented over the course of several years with a chronic nonhealing left posterior scalp wound. A car hit the patient when he was 2 years old and injured the scalp in the location of the skin lesion. Multiple wound cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and biopsies were consistent with botryomycosis. He was treated with multiple surgical debridements, skin grafts, and various courses of oral and intravenous antibiotics with slight improvement. One reason for poor response to therapy was noncompliance with long-term home antibiotics. The most recent tissue culture grew MRSA in addition to Nocardia mexicana, and he experienced improvement on linezolid and minocycline. Although it is important to exclude nocardiosis and actinomycosis when diagnosing botryomycosis, our patient was diagnosed with botryomycosis after multiple biopsies and positive MRSA cultures 2 years prior to 1 positive N mexicana culture. Our case is a unique presentation of botryomycosis in an individual who subsequently developed Nocardia-positive wound cultures.

Filiform Verrucous Sarcoidosis of the Face: A Warty Report

Sarcoidosis is a multisystem inflammatory condition of unknown etiology. Variability in the cutaneous features of sarcoidosis is profound, and its protean manifestations affirm the condition’s designation as one of dermatology’s “great mimics.” Cutaneous phenotypes of sarcoidosis include but are by no means limited to ichthyosiform, alopecic, erythrodermic, angiolupoid, and verrucous variants. Verrucous sarcoidosis is an exceedingly rare manifestation, and previous reports of this phenotype are limited to 15 cases. Most cases in the extant literature presented on the extremities, with clinical features mimicking that of a common wart, or as verrucous crateriform nodules, ulcers, or cutaneous horns. Only 4 previous reports of facial verrucous sarcoidosis exist in the literature, and to our knowledge, no prior cases have demonstrated filiform lesion morphology. Here we present a case of filiform verrucous sarcoidosis in an otherwise healthy, middle-aged African American man, devoid of internal organ involvement and limited to the face, histopathologically confirmed by the presence of characteristic granulomata devoid of lymphocytic infiltrates.

Identification of Nocardia mexicana Using Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS) and Treatment

Our dermatology clinic and our hospital that we are associated with send tissue culture specimens to an outside microbiology laboratory for identification. We contacted the laboratory, and they reported using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and the conventional phenotypic method to identify the organism in our tissue specimen. MALDITOF MS is a time-efficient method of identifying Nocardia species, and according to Khot et al, this method identified 94.8% and 83.1% of the isolates to the genus and species levels, respectively. Based on this process, the tissue culture was reported as Nocardia mexicana with resistance to doxycycline and trimethoprim-sulfamethoxazole. We used this information from the report to treat our patient with appropriate antibiotics with improvement in condition.

Case Report of Onychomycosis and Tinea Corporis Due to Microsporum gypseum

Background: Microsporum gypseum is a geophilic dermatophyte that colonises keratinous substances in the soil. Fur-bearing animals carry this dermatophyte but are rarely infected. Human infection can be acquired from the soil, carrier or infected animals, and rarely other humans. M gypseum is an uncommon cause of cutaneous infection in humans and typically manifests as tinea corporis, tinea barbae, and tinea capitis. Onychomycosis is rarely caused by M gypseum. Case Summary: We present a case of a 32-year-old white man who presented with a red scaly rash and nail dystrophy after adopting a pet rat 10 years prior to presentation. A fungal culture of a nail clipping grew out M gypseum, and the patient was treated with terbinafine daily for 6 weeks for dystrophic onychomycosis and tinea corporis. After the 6 weeks of treatment, the erythema at the proximal nail fold and distal finger had improved but still persisted. An additional 6 weeks of terbinafine daily completely resolved the clinical manifestations of onychomycosis. Conclusion: The increase in incidence of M gypseum onychomycosis over the past 2 decades is thought to be due to phylogenetic evolution of the dermatophyte from soil saprophyte to a human parasite. Increasing domestication of mammals is also thought to contribute to increasing incidence. Treatment consists of an extended course of terbinafine or itraconazole.

JAAD Grand Rounds quiz∗: Dusky intertriginous plaques and acral erythema after bone marrow transplant

LEARNING OBJECTIVES At the conclusion of this learning activity, physician participants should be able to assess their own diagnostic and patient management skills and use the results of this exercise to help determine personal learning needs that can be addressed through subsequent CME involvement. Instructions for claiming CME credit appear in the front advertising section. See last page of Contents for page number. INSTRUCTIONS In answering each question, refer to the specific directions provided. Because it is often necessary to provide information occurring later in a series that give away answers to earlier questions, please answer the questions in each series in sequence.