Patient Initiated Store and Forward Teledermatology: A Single Practice Experience.

We report a retrospective chart review of 112 images submitted from 85 patients through the Epic electronic medial record to determine disposition of patient complaints and to estimate cost savings. The study represents a single practice at a tertiary care university practice. Sixty (53.6%) were resolved electronically. The remaining 52 (46.4%) were deemed to require an in-person office visit. Of the 60 electronically resolved, 23 (38.3%) involved reassurance of a self-limited condition while 37 (61.7%) involved prescription management. The encounters resolved through MyChart were not billed and provided a cost savings of $2,052.29 and $4,664.96 for Level 3 and 4 office visit equivalents, respectively, for a total of $6,717.25. Patients needing an office visit were on average seen 18.3 days from the date of photo submission. After adjusting for patient-initiated rescheduling of the earliest appointment date provided, this was slightly reduced to 16.0 days. We observed diagnostic concordance in 88/112 (78.6%) eConsults. Krippendorff's alpha was 0.773 (95% confidence interval of 0.691- 0.846), indicating a tentative conclusion of modest reliability between the two raters.5 Concordance regarding the need for an appointment as determined by the two raters was observed in 71/112 (63.4%) eConsults. We conclude that patient-submitted eConsults is a viable means of resolving just over half of patient-submitted dermatologic concerns while offering cost savings; there is modest inter-rater reliability.

A case of severe nivolumab-induced lichen planus pemphigoides in a child with metastatic spitzoid melanoma.

Dermatologic reactions are among the most common adverse events of antiprogrammed cell death-1 (anti-PD-1) monoclonal antibodies agents and include maculopapular rash, psoriasiform rash, lichenoid eruptions, autoimmune bullous disorders, and vitiligo. Here, we present a case of a 12-year-old African American male with metastatic spitzoid melanoma treated with nivolumab who developed a mild lichenoid eruption that progressed to a severe case of lichen planus pemphigoides (LPP). Management was complex given the patient's age and history and included hospitalization for intravenous steroids, an intensive topical steroid regimen, methotrexate, and discontinuation of nivolumab. This case illustrates a rare but dramatic progression from a mild LP-like eruption to severe bullous lichenoid eruption, most consistent with LPP, as well as the diagnostic and treatment challenges in the setting of a pediatric patient on nivolumab.

Clinical Characteristics, Disease Course, and Outcomes of Patients With Acute Generalized Exanthematous Pustulosis in the US.

Importance: Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series. Objective: To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US. Design, Setting, and Participants: A retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included. Main Outcomes and Measures: Patient demographic characteristics, clinical course, suspected causative agent, treatment, and short- and long-term outcomes. Results: Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 °C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were ß-lactam antimicrobials, 51 (33.8%) were non-ß-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (n = 12), none of which was suspected to be due to AGEP. Conclusions and Relevance: This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.

Evaluation of a Case Series of Patients With Generalized Pustular Psoriasis in the United States.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP-specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.

Evaluation of a Case Series of Patients With Palmoplantar Pustulosis in the United States.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

Pyoderma gangrenosum associated with levamisole-adulterated cocaine in a c-ANCA positive patient.

Pyoderma gangrenosum (PG) is an inflammatory, ulcerative condition that is characterized by painful ulcers that commonly present on the lower extremities. Up to half of PG cases are associated with underlying systemic disease, including inflammatory bowel disease, various autoimmune conditions, and malignancy. Another well-known association is the manifestation of PG with recreational cocaine use, especially cocaine contaminated with the adulterant agent levamisole. Once utilized for its immunomodulatory capabilities, levamisole was withdrawn from the market in 2002. It has since been repurposed to potentiate the amphetamine-like effects and duration of cocaine and has reduced preparation cost. We present a 52-year-old woman with chronic maxillary sinusitis and cocaine use disorder presenting with a two-week history of painful ulcers on bilateral lower extremities, each with a purulent base and undermined, violaceous borders. Urine toxicology was positive for cocaine and serologic studies were positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and lupus anticoagulant. Underlying conditions, especially that of granulomatosis with polyangiitis, were considered and ultimately ruled out. The patient's lesions exhibited a marked response with a short course of oral corticosteroids, typical of PG associated with levamisole. This case highlights the crucial role that drug abstinence plays in the prevention of recurrence.

Putting the Pieces Into Place: A Case of Systemic Polyarteritis Nodosa.

This is a case of systemic polyarteritis nodosa (PAN) in a 43-year-old male who initially presented to the hospital with a puzzling collection of signs and symptoms, including fever, arthralgias, myalgias, abdominal pain, dark urine, and rash. His illness evolved over the course of four weeks, and skin biopsy helped to clinch the diagnosis and lead to appropriate treatment. It is important to consider systemic PAN in the work-up of patients with subtle skin findings in the context of seemingly unrelated constitutional, abdominal, genitourinary, cardiac, and neurological signs and symptoms.

A 23-Year-Old Man with Hyper-IgM Syndrome Presenting with Asymptomatic Violaceous Facial Plaques.

Tumid lupus is a rare subtype of chronic cutaneous lupus that is characterized by urticaria-like photosensitive plaques. Unlike discoid lupus, it has minimal to no surface change and resolves without scarring. On pathological examination, it may be distinguished from other types of lupus by abundant interstitial mucin deposits. Herein, we describe a case of tumid lupus in a 23-year-old Kuwaiti male with hyper-IgM syndrome. To our best knowledge, this is the first report of tumid lupus in a patient with a primary immunodeficiency.

Acquired acrodermatitis enteropathica after gastric bypass surgery responsive to IV supplementation.

Nutritional deficiency is rare in developed countries, but can be acquired from decreased nutrient intake, reduced absorption, and increased gastrointestinal excretion. We report a patient with acquired acrodermatitis enteropathica (AE) who exhibited low plasma zinc levels and concurrent nutritional deficiencies (pyridoxine, selenium and fatty acids). Our patient had undergone Roux-en-Y gastric bypass 13 years prior to presentation. The rash, consistent with AE clinically and histologically, nearly resolved one week after starting IV zinc supplementation, total parenteral nutrition, and micronutrient supplements. This case highlights the importance of long-term post-operative follow-up for gastric bypass patients who are at high risk for micronutrient and macronutrient deficiencies and illustrates the potential for rapid improvement with IV supplementation.

Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne.

IMPORTANCE: Spironolactone has been shown to be an effective treatment option for hormonally mediated acne but can cause hyperkalemia. The prevalence of hyperkalemia among healthy young women taking spironolactone for acne is unclear. OBJECTIVE: To measure the rate of hyperkalemia in healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of healthy young women taking spironolactone for acne. Data from December 1, 2000, through March 31, 2014, were obtained from a clinical data repository. Outpatient data were collected from 2 tertiary care centers in the United States. We analyzed rates of hyperkalemia in 974 healthy young women taking spironolactone for acne. We also analyzed 1165 healthy young women taking and not taking spironolactone to obtain a profile for the baseline rate of hyperkalemia in this population. Exclusion criteria were cardiovascular disease, renal failure, and the use of medications that affect the renin-angiotensin-aldosterone system. MAIN OUTCOMES AND MEASURES: The rate of hyperkalemia in healthy young women taking spironolactone for acne was calculated. Secondary measures included spironolactone prescriber profiles and potassium monitoring practices. RESULTS: There were 13 abnormal serum potassium measurements in 1802 measurements obtained among young women receiving spironolactone therapy, yielding a hyperkalemia rate of 0.72%, equivalent to the 0.76% baseline rate of hyperkalemia in this population. Repeat testing in 6 of 13 patients demonstrated normal values, suggesting that these measurements may have been erroneous. In the remaining 7 patients, no action was taken. CONCLUSIONS AND RELEVANCE: The rate of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this population. Routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne.

Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1.

The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.

Novel oral anticoagulants: what dermatologists need to know.

The development of novel oral anticoagulants provides clinicians and patients a welcome alternative to the challenges of warfarin therapy. Dermatologists must be aware of the potential impact of novel oral anticoagulants on their surgical and medical practice. This review provides a concise summary of the novel oral anticoagulants for dermatologists with particular emphasis on: (1) the pharmacokinetic properties of these drugs and how they differ from warfarin, (2) suggested management during cutaneous surgery, (3) adverse drug interactions with commonly prescribed medications in dermatology, and (4) potential use within dermatology for treatment of disorders of cutaneous thrombosis.

Giant pyogenic granuloma in a patient with chronic lymphocytic leukemia.

Pyogenic granuloma, also known as lobular capillary hemangioma, is a common benign vascular proliferative lesion that can present at any age on the skin or mucous membranes. Most lesions do not exceed 2 cm, but there are a handful of giant cutaneous pyogenic granulomas that have been reported, often in individuals with underlying immune dysfunction. Here, we report the first giant pyogenic granuloma in a patient with a hematological malignancy, chronic lymphocytic leukemia.

Reconstitution of the mitochondrial calcium uniporter in yeast.

The mitochondrial calcium uniporter is a highly selective calcium channel distributed broadly across eukaryotes but absent in the yeast Saccharomyces cerevisiae. The molecular components of the human uniporter holocomplex (uniplex) have been identified recently. The uniplex consists of three membrane-spanning subunits--mitochondrial calcium uniporter (MCU), its paralog MCUb, and essential MCU regulator (EMRE)--and two soluble regulatory components--MICU1 and its paralog MICU2. The minimal components sufficient for in vivo uniporter activity are unknown. Here we consider Dictyostelium discoideum (Dd), a member of the Amoebazoa outgroup of Metazoa and Fungi, and show that it has a highly simplified uniporter machinery. We show that D. discoideum mitochondria exhibit membrane potential-dependent calcium uptake compatible with uniporter activity, and also that expression of DdMCU complements the mitochondrial calcium uptake defect in human cells lacking MCU or EMRE. Moreover, expression of DdMCU in yeast alone is sufficient to reconstitute mitochondrial calcium uniporter activity. Having established yeast as an in vivo reconstitution system, we then reconstituted the human uniporter. We show that coexpression of MCU and EMRE is sufficient for uniporter activity, whereas expression of MCU alone is insufficient. Our work establishes yeast as a powerful in vivo reconstitution system for the uniporter. Using this system, we confirm that MCU is the pore-forming subunit, define the minimal genetic elements sufficient for metazoan and nonmetazoan uniporter activity, and provide valuable insight into the evolution of the uniporter machinery.

MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling.

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.