Dermatology Online Journal is an open-access, refereed publication intended to meet reference and education needs of the international dermatology community since 1995. Dermatology Online Journal is supported by the Department of Dermatology UC Davis, and by the Northern California Veterans Administration.
Volume 25, Issue 7, 2019
A review of next generation sequencing technologies used in the evaluation of the skin microbiome: what a time to be alive
The role of the microbiome in healthy and disease states of the human body is progressively being found to extend beyond the gastrointestinal tract and into other organ systems such as the skin. Researching the microbiome thus has become paramount to understanding additional physiological and pathophysiological mechanisms that may be at play between microbes and their hosts. Cell cultures have traditionally been used to study the microbiome, but in our current day and age, advanced metagenomic techniques - such as 16S rRNA amplicon sequencing and whole metagenomic shotgun sequencing - are better able to classify the microorganisms making up the microbiome. Utilizing metagenomics alone, however, does not allow for the study of the more complex effects of the microbiome, such as changes in gene expression and metabolic byproducts. Thus, incorporation of other modalities such as metatranscriptomics, metaproteomics, and metabolomics are needed to further elucidate the extensive intricacies of the skin microbiome.
The current standard of care for high-risk melanoma patients is a two-step process using Total Body Photography (TBP) followed by dermoscopy and is limited to a select group of patients. Methods: A cross-sectional study of patient characteristics and self-reported melanoma risk factors associated with TBP usage and pathology-confirmed outcomes was conducted on a sample of 4,692 patients in a single practitioner private dermatology setting. Results: TBP patients were significantly more likely to be male, partnered, tobacco users, highly educated, and have increased self-reported risk factors (such as fair skin, personal history of skin cancer or melanoma, family history of skin cancer, numerous moles, or previous history of sunburn, P<0.05). Personal history of skin cancer and melanoma, male gender, ?40 moles, Medicare insurance, and increasing age were positively associated with malignancy outcomes, whereas higher education, family history of melanoma, and traditional (private) insurance were associated with reduced prevalence of malignant lesions. Patients' self-assessed skin cancer risk and access to skin detection modalities can result in detection of melanoma at early, curable stages. Higher level of education and partner status may result in a greater awareness of risk factors associated with melanoma.
Onychomycosis is a prevalent disease of the nail. Traditional methods for diagnosis include direct microscopy with potassium hydroxide (KOH microscopy) and fungal culture. Other techniques using histochemical staining have higher sensitivity, but cannot identify genus or species of the infecting agent. PCR assays are sensitive, specific, and capable of genus and species level identification. We describe a real-time PCR assay for 15 different fungi that are associated with onychomycosis. Of 425 clinical samples suspected of onychomycosis analyzed by fungal culture and PCR, 219 samples were positive for both (52% agreement). Of the 206 discordant samples, 95% were resolved in favor of PCR by DNA sequencing. On a larger data set of 2,452 samples, positivity rates for histopathology, PCR, and culture were 85%, 73%, and 54% respectively. Further, 48% of PCR positive and 51% of histopathology positive samples were negative by culture. PCR outperformed culture compared to histopathology for sensitivity (80% versus 49%), specificity (92% versus 79%), positive predictive value (94% versus 77%), and negative predictive value (76% versus 52%). These results indicate the culture method lacks the sensitivity to be a reliable assay for onychomycosis, that PCR and histopathology are highly concordant, and that PCR provides the highest degree of diagnostic accuracy available.
Ultraviolet (UV) radiation is associated with negative health effects, including sun damage and skin cancer. The purpose of this study is to compare the protective effects of the shade provided by a sun umbrella versus that provided by a tree. Sun sensors that register the level and dose of UV radiation were placed in the shade and in direct sunlight. Measurements were recorded every half hour between the hours of 12:30 p.m. and 3:00 p.m. in Sacramento, California. The results suggest that the level of UV radiation in the shade is not zero. The sensors located in tree shade indicated that over 5% of UV radiation was detected in the shade. The sensors located in sun-umbrella shade showed that greater than 17% of UV radiation reached the shade. The sun sensors used in our study collected UV radiation data relevant to UV index; however, they did not differentiate between UVA, UVB, visible, and infrared light. The amount of UV radiation detected in the shade is not zero, thus regular sunscreen use and other sun protective practices should be followed to reduce the risk of sun damage and skin cancer.
Granulomatous slack skin (GSS) is a rare subtype of mycosis fungoides. It usually presents as slowly evolving, erythematous, slack plaques that usually involve folds of lax skin. Herein, we report a case of GSS and we show electron microscopy examination. Atypical T cells with convoluted and cerebriform nuclei, lymphophagocytosis, and elastophagocytosis are key features of GSS under electron microscopy.
Epidermotropic CXCR3 positive marginal zone lymphoma: a distinctive clinical histopathological entity potentially originating in the skin; it does not always indicate splenic marginal zone lymphoma
Epidermotropic B cell lymphoma represents a rare form of marginal zone lymphoma presenting as a disseminated skin rash resembling pityriasis rosea. To date there are 8 reported cases. In addition to the widespread nature of the skin rash, there is a proclivity for spleen and bone marrow involvement raising consideration regarding its categorization as a systemic lymphoma. We present an 89-year-old man with epidermotropic B cell lymphoma, who presented with a pityriasis rosea-like skin rash. An initial diagnosis of diffuse large cell B cell lymphoma was made based on the extent of dermal-based large cell infiltration. However, after recognizing the epidermotropic component and the distinctive clinical presentation, a diagnosis of epidermotropic B cell lymphoma was rendered. There was minimal bone marrow involvement based only on flow cytometric analysis, but there was no apparent bone marrow or splenic involvement on routine light microscopic assessment. Remission was = achieved with single agent rituximab chemotherapy and the patient remained symptom free. The neoplastic CD20 positive epidermotropic B lymphocytes expressed CXCR3. Similar to the prior reported cases by the authors, the neoplastic cells expressed CXCR3, a chemokine whose organ and tissue specific ligands could contribute to its relatively indolent clinicalcourse.
Follicular porokeratosis is a rare variant of porokeratosis in which the coronoid lamellae are confined to hair follicles. It classically presents with annular plaques with a surrounding keratotic ridge. However, the clinical presentation has shown significant variation in reported cases. We present the case of a 26-year-old man with chronic diffuse follicular spicules associated with alopecia. Clinical findings were suggestive of trichodysplasia spinulosa, but multiple biopsies showed findings consistent with follicular porokeratosis. Diffusely spiculated presentation as present in our patient has not been previously reported in the literature. It is important to recognize the necessity of histopathologic confirmation in a diagnostically challenging condition such as follicular porokeratosis.
Two siblings affected by Netherton/Comèl syndrome. Diagnostic pathology and description of a new SPINK5 variant
Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene encompassing three main clinical findings: 1) ichthyosiform dermatitis and/or ichthyosis linearis circumflexa, 2) hair shaft defects with peculiar "trichorrhexis invaginata" (bamboo pole hair) findings, 3) atopic dermatitis. We describe two siblings affected by Netherton/Comèl syndrome who were referred to our Center for Genodermatosis. A diagnostic pathway and the description of a new SPINK5 variant has been determined for these two patients. A novel genetic mutation has been found.
Juvenile hyaline fibromatosis is a recessive autosomal hereditary disorder characterized by abnormal growth of hyalinized fibrous tissue. Its clinical presentation is marked by tumors of the skin, bone lesions, joint contractures, and gingival hyperplasia. We report a localized form of juvenile hyaline fibromatosis, a rare disease with several cases reported in the worldwide literature. A 23-year-old man presented with multiple tumors, joint contractures, and osteolytic bone lesions, but without gingival hyperplasia in one year of follow-up. Although, the onset of this condition is commonly in early childhood with progression, his unusual clinical presentation began at eight years of age with late progression in adolescence.
Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkin lymphoma often accompanied by autoimmune and paraneoplastic phenomena. Up to 50% of patients with AITL present with skin manifestations. This case series highlights two cases of AITL presenting with unusual cutaneous findings: one with a medium-vessel vasculitis and another with a chronic urticarial eruption. Clinicians should consider AITL in the differential diagnosis of vasculitis or urticaria refractory to standard treatment.
The mechanism underlying frontal fibrosing alopecia (FFA) is unknown, but proposed mechanisms share commonality of T cell-mediated destruction of the hair follicle bulge. IL-12 and IL-23 are key cytokines involved in CD4 T cell differentiation towards Th1 and Th17 phenotypes. We present a 62-year-old woman who developed persistent FFA while on ustekinumab for treatment of preexisting psoriasis. This case presents evidence against Th1 and Th17 pathways as essential to pathogenesis in FFA. This case also suggests that IL-12 and IL-23 inhibition is ineffective for this form of scarring alopecia.
Tiger-like mycosis fungoides: an unusual clinical presentation of a rare variant of mycosis fungoides.
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. Mycosis fungoides classically presents in the skin as patches, plaques, tumors, or erythroderma, progressing to involve the lymph nodes and peripheral blood. The many clinical variants, with different histologic patterns, and the subtle early clinical and histologic changes may delay early diagnosis and present a diagnostic challenge for clinicians. The greatest challenge in diagnosis is the pre-mycotic stage, which may closely resemble eczematous or psoriasiform dermatitis clinically and histologically. The persistence of lesions and inadequate response to treatment are the first warning signs. Later stages of MF have a poor prognosis with poor therapeutic response and fatal outcome. We describe a 72-year-old man, who presented with a two-year history of an unusual eruption, which started on the abdomen, around the waistline, and gradually spread to involve his back, trunk, and buttocks. Clinically, the skin eruption presented as tiger-like stripes. The diagnosis was confirmed after histopathologic examination. The patient was treated with NB-UVB phototherapy with marked improvement.
Interstitial granulomatous drug reaction is a rare condition presenting as erythematous-to-violaceous plaques on the lateral trunk, axillae, buttocks, and thighs. Calcium-channel blockers, angiotensin converting enzyme inhibitors, beta-blockers, and statins have been described as drugs that can trigger interstitial granulomatous drug reaction. We present a case of interstitial granulomatous drug reaction related to hydrochlorothiazide and our approach to management of this condition. The diagnosis was confirmed with a skin biopsy and a rechallenge of hydrochlorothiazide, which exacerbated the patient's symptoms. The patient improved significantly with rigorous photoprotection, combination dapsone-alitretinoin therapy, and discontinuation of hydrochlorothiazide.
We describe adult-onset Kawasaki disease (KD) and review clinical manifestations and treatment guidelines. Our patient is a 20-year-old female who initially presented to an outside hospital for fever, cervical lymphadenopathy, malaise, exudative tonsillitis, and skin eruption. She received antibiotics for suspected exudative pharyngitis, but experienced continued fevers and presented to the UCLA emergency room one week later. She had diffuse petechial macules coalescing into reticulated patches, fingertip peeling, conjunctival injection, oral erosions, and tongue swelling. Despite her age, given her constellation of symptoms, a diagnosis of typical KD was favored. She was started on high dose aspirin and IVIG, with improvement of rash and conjunctivitis. She was discharged on 325mg of aspirin daily with close follow-up. This case highlights the challenge of diagnosing KD in adults. Although this patient had classic symptoms, she was likely misdiagnosed because KD is rare in adults and without validated criteria. Our patient met the pediatric criteria, suggesting these should be considered when clinical suspicion for adult-onset KD is high. Adult-onset KD is most commonly misdiagnosed as toxic shock syndrome or drug-induced hypersensitivity syndrome and these are important to rule-out. Treatment with high-dose aspirin and IVIG is well established and should be initiated promptly.
Undifferentiated pleomorphic sarcoma presenting as an exophytic pedunculated tumor on the left scapula
Undifferentiated pleomorphic sarcoma is a common soft tissue sarcoma. Unfortunately, any attempt to describe the line of differentiation fails. It represents a final common pathway in tumors that undergoes progression towards dedifferentiation. We report a man with an undifferentiated pleomorphic sarcoma presenting as an exophytic pedunculated tumor of the left scapula. Histopathology analysis revealed spindle-shaped cells with great pleomorphism and numerous mitoses. Immunohistochemistry showed diffuse expression of vimentin. Wide local excision was performed after an oncology consultation. After two-years of follow-up, the patient has shown no evidence of recurrence or metastases.
Numerous studies have suggested a correlation between oral health, the oral microbiome, and various dermatologic conditions, particularly psoriasis. In this study, we utilize a specially designed questionnaire administered to 265 patients at The Ohio State University's dermatology clinics to explore the relationship between psoriasis and a combination of factors that included dietary habits, oral health, and oral hygiene practices. Age, family history of psoriasis, previous diagnosis of strep throat or rheumatoid arthritis, and oral pain or discomfort experienced within the last 12 months were all found to be significant predictors of psoriasis. Additionally, higher body mass index scores, poor gum health, and speech difficulties related to dental problems were all correlated with more severe psoriasis symptoms. Conversely, patients who reported consuming fresh fruit at least once a day experienced milder symptoms. Our goal is to develop a better understanding of how and why psoriasis incidence is correlated with some of the oral health factors under review.