IgG memory B cells expressing IL4R and FCER2 are associated with atopic diseases.

BACKGROUND: Atopic diseases are characterized by IgE antibody responses that are dependent on cognate CD4 T cell help and T cell-produced IL-4 and IL-13. Current models of IgE cell differentiation point to the role of IgG memory B cells as precursors of pathogenic IgE plasma cells. The goal of this work was to identify intrinsic features of memory B cells that are associated with IgE production in atopic diseases. METHODS: Peripheral blood B lymphocytes were collected from individuals with physician diagnosed asthma or atopic dermatitis (AD) and from non-atopic individuals. These samples were analyzed by spectral flow cytometry, single cell RNA sequencing (scRNAseq), and in vitro activation assays. RESULTS: We identified a novel population of IgG memory B cells characterized by the expression of IL-4/IL-13 regulated genes FCER2/CD23, IL4R, IL13RA1, and IGHE, denoting a history of differentiation during type 2 immune responses. CD23+ IL4R+ IgG+ memory B cells had increased occurrence in individuals with atopic disease. Importantly, the frequency of CD23+ IL4R+ IgG+ memory B cells correlated with levels of circulating IgE. Consistently, in vitro stimulated B cells from atopic individuals generated more IgE+ cells than B cells from non-atopic subjects. CONCLUSIONS: These findings suggest that CD23+ IL4R+ IgG+ memory B cells transcribing IGHE are potential precursors of IgE plasma cells and are linked to pathogenic IgE production.

Assessing the use of methotrexate as an alternate therapy for pemphigus vulgaris and pemphigus foliaceus.

Methotrexate is historically recognized as an effective treatment of pemphigus but its utility as a single or alternate steroid-sparing agent was not recognized in recent consensus recommendations in pemphigus management. We aimed to evaluate the efficacy and safety of a treatment course for pemphigus that involves methotrexate as a single or steroid-sparing agent. In a retrospective cohort study, we examined patients with pemphigus vulgaris or pemphigus foliaceus who were on ≥3 months of methotrexate therapy. Efficacy and safety were evaluated by established pemphigus disease endpoints. Of the 34 patients who met inclusion criteria, 25 (73.5%) were on glucocorticoids at time of methotrexate initiation (median follow-up: 5.4 years; median time on methotrexate: 3.7 years). An appreciable proportion achieved disease control (91.2%), with some achieving clinical remission off all systemic therapies (23.5%). For patients on glucocorticoids, median time to control was 42 days, median time to minimal steroid dose tapering (5 mg prednisone) was 161 days, and median time to complete steroid tapering was 308 days. For patients on methotrexate as a single agent, median time to control was 119 days. Among all patients, relapse commonly occurred (88.2%). At last follow-up, 26.5% were managed on topical therapies alone and 11.8% required systemic steroid therapy. Methotrexate was largely tolerated with a low incidence of adverse events leading to treatment discontinuation (2.9%). Methotrexate has the potential to be an effective and well-tolerated option for patients and may be considered for use as an alternate single or steroid-sparing agent for pemphigus.

The Use of Mycophenolate Mofetil in the Treatment of Bullous Pemphigoid.

BACKGROUND: The first-line treatment for patients with bullous pemphigoid (BP), the most common autoimmune blistering disease, is systemic glucocorticoids, which are associated with numerous side effects. Mycophenolate mofetil (MMF) may be beneficial in BP as a steroid-sparing alternative; however, evidence is limited. OBJECTIVES: To evaluate the efficacy and safety of MMF in patients with BP. METHODS: In this retrospective chart review, records of patients with BP treated with MMF alone or in combination with prednisone, who presented between 2013 and 2017, were analyzed. RESULTS: Twenty-six patients were included. Twelve patients were treated with MMF alone (monotherapy) and fourteen were treated with MMF and prednisone concomitantly at some point during their treatment course (dual therapy). Improvement in BP was observed in 26 (100%) patients with MMF therapy. Mean time to improvement was 0.8 months. Twenty-five (96.2%) patients [11/12 (91.7%) on monotherapy and 14/14 (100%) on dual therapy] achieved complete control of their disease. Mean time to complete control amongst all patients was 5.6 months. Twelve (46.2%) patients [4/12 (33.3%) on monotherapy and 8/14 (57.1%) on dual therapy] experienced disease remission with no subsequent flares for up to 15 months after MMF was discontinued. Twelve mild adverse effects were reported with one individual discontinuing therapy due to gastrointestinal symptoms. No serious adverse effects were reported. CONCLUSION: MMF is a safe and effective therapy for BP and can yield improvement and complete response in most patients and remission in some. J Drugs Dermatol. 2022;21(2):151-155. doi:10.36849/JDD.6042.

Vesiculobullous Darier Disease Symptomatically Responsive to Cetirizine

Darier disease is an autosomal dominant genodermatosis of abnormal keratinization characterized by hyperkeratotic papules and plaques with a predilection for seborrheic areas. We report a case of a rare vesiculobullous variant of treatment-resistant Darier disease in a 55-year-old woman that failed topical tacrolimus and topical and oral glucocorticoids. Cetirizine was initiated at 10 mg daily and increased to 40 mg daily over four weeks, with resultant marked improvement of the patient's burning sensation. A punch biopsy revealed a perivascular infiltrate of eosinophils. This patient's symptomatic improvement with cetirizine, which has antagonizing properties against eosinophils, highlights the potential role of eosinophils in the pathogenesis of vesiculobullous Darier disease. We suggest that major basic protein secreted by eosinophils may propagate blister formation in vesiculobullous Darier disease by disrupting desmosomes. J Drugs Dermatol. 2019;18(2):213-214.

Disparity in Cutaneous Pigmentary Response to LED vs Halogen Incandescent Visible Light: Results from a Single Center, Investigational Clinical Trial Determining a Minimal Pigmentary Visible Light Dose.

Background: While most of the attention regarding skin pigmentation has focused on the effects of ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported. OBJECTIVE: The purpose of this study was to investigate the cutaneous pigmentary response to pure visible light irradiation, examine the difference in response to different sources of visible light irradiation, and determine a minimal pigmentary dose of visible light irradiation in melanocompetent subjects with Fitzpatrick skin type III - VI. METHODS: The study was designed as a single arm, non-blinded, split-side dual intervention study in which subjects underwent visible light irradiation using LED and halogen incandescent light sources delivered at a fluence of 0.14 Watts/cm2 with incremental dose progression from 20 J/cm2 to 320 J/cm2. Pigmentation was assessed by clinical examination, cross-polarized digital photography, and analytic colorimetry. RESULTS: Immediate, dose-responsive pigment darkening was seen with LED light exposure in 80% of subjects, beginning at 60 Joules. No pigmentary changes were seen with halogen incandescent light exposure at any dose in any subject. CONCLUSION: This study is the first to report a distinct difference in cutaneous pigmentary response to different sources of visible light, and the first to demonstrate cutaneous pigment darkening from visible LED light exposure. Our findings raise the concern that our increasing daily artificial light surroundings may have clandestine effects on skin biology.

J Drugs Dermatol. 2017;16(11):1105-1110.

A Difference in Cutaneous Pigmentary Response to LED Versus Halogen Incandescent Visible Light: A Case Report from a Single Center, Investigational Clinical Trial Determining a Minimal Pigmentary Visible Light Dose.

BACKGROUND: While most of the attention regarding skin pigmentation has focused on the effects on ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported. In this report, we describe a case of painful erythema and induration that resulted from direct irradiation of UV-naïve skin with visible LED light in a patient with Fitzpatrick type II skin.

METHODS AND RESULTS: A 24-year-old healthy woman with Fitzpatrick type II skin presented to our department to participate in a clinical study. As part of the study, the subject underwent visible light irradiation with an LED and halogen incandescent visible light source. After 5 minutes of exposure, the patient complained of appreciable pain at the LED exposed site. Evaluation demonstrated erythema and mild induration. There were no subjective or objective findings at the halogen incandescent irradiated site, which received equivalent fluence (0.55 Watts / cm2). The study was halted as the subject was unable to tolerate the full duration of visible light irradiation.

CONCLUSION: This case illustrates the importance of recognizing the effects of visible light on skin. While the vast majority of investigational research has focused on ultraviolet light, the effects of visible light have been largely overlooked and must be taken into consideration, in all Fitzpatrick skin types.

J Drugs Dermatol. 2017;16(4):388-392.

Local heat urticaria.

We present a 38-year-old woman with local heat urticaria confirmed by heat provocation testing. Heat urticaria is a rare form of physical urticaria that istriggered by exposure to a heat source, such as hot water or sunlight. Although it is commonly localized and immediate, generalized and delayed onset forms exist. Treatment options include antihistamines and heat desensitization. A brisk, mechanical stroke elicited a linear wheal. Five minutes after exposure to hot water, she developed well-demarcated,erythematous blanching wheals that covered the distal forearm and entire hand.

Acquired aquagenic papulotranslucent acrokeratoderma.

Aquagenic papulotranslucent acrokeratoderma isa rare condition with the development of white-totransluscentpapules and plaques after exposureto water. While the first report was described asan autosomal dominant hereditary condition,there have since been acquired cases reported inassociation with cystic fibrosis, with prior exposureto a drug, or as an idiopathic condition. We presenta 24-year-old man with acquired aquagenicpapulotranslucent acrokeratoderma that has beenpresent since infancy, without a family history,without prior drug exposure, and without anypersonal or family history of cystic fibrosis. Thus fartreatment with urea cream, calipotriene ointment,vitamin E cream, and clobetasol ointment hasbeen ineffective. Our patient will be treated withbotulinum toxin.

Multiple pilomatricomas in the setting of myotonic dystrophy.

The association between multiple pilomatricomasand the autosomal dominant neurodegenerativedisorder myotonic dystrophy has been described inthe literature. Although the mechanism is unknown,it is hypothesized that the dystrophia myotonicaprotein kinase mutation in myotonic dystrophyaffects intracellular calcium levels, which alterproliferation and terminal differentiation that leads tocells that are observed in pilomatricomas. We presenta patient with multiple, symptomatic pilomatricomasand myotonic dystrophy, with a strong family historyof both of these rare disorders.

Eosinophilic dermatosis of hematologic malignancy.

We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation. Patientswho develop EDHM should undergo prompthematologic/oncologic evaluation.

Possible photoactivated dermatitis with features of post-inflammatory pigmentary alteration (PIPA) and rosacea.

Cutaneous flushing and facial erythema are common dermatologic conditions that elicit a wide differential diagnosis that includes rosacea, seborrheic dermatitis, photodermatitis, connective-tissue diseases, carcinoid syndrome, and mastocytosis. Herein we present an usual case of a mask-like rosacea-PIPA overlap that occurred in a patient with prior history of rectal carcinoid tumor and a negative systemic evaluation.

Chronic actinic dermatitis occurring in an adult with atopic dermatitis.

Chronic actinic dermatitis (CAD) is a photosensitivity disorder that is characterized by a persistent eczematous eruption in sun-exposed sites. The hallmark of CAD is a reduced minimal erythema dose (MED) to ultraviolet B (UVB), ultraviolet A (UVA), and/or to visible light, which makes phototesting the essential diagnostic investigation. The uncommon subgroup of patients with atopic dermatitis (AD) that are affected by CAD has primarily been described in young patients in the United Kingdom. We present an atopic adult women with CAD who was diagnosed years after symptoms began. We believe it is important that dermatologists perform phototests on AD patients with features of a photoaggravated dermatitis in order to avoid delay in diagnosis of a true photosensitivity condition and provide appropriate management.

The use of mycophenolate mofetil for the treatment of autoimmune and chronic idiopathic urticaria: experience in 19 patients.

BACKGROUND: There is a paucity of investigation on which to base the treatment of chronic urticaria after a patient fails maximum therapy with antihistamines. One prospective, open-label, uncontrolled study suggested that mycophenolate mofetil may be a successful second-line therapy. OBJECTIVE: We sought to evaluate the efficacy and safety of mycophenolate mofetil in 19 patients with autoimmune and chronic idiopathic urticaria. METHODS: In a retrospective chart review, records of patients with autoimmune and chronic idiopathic urticaria who were evaluated between 2001 and 2009 were analyzed. RESULTS: Improvement in urticaria was observed in 89% of patients, specifically 91% of patients with autoimmune urticaria and 88% with chronic idiopathic urticaria. Time to initial improvement ranged from 1 to 9 weeks. In 59% of these patients, complete control of urticaria was achieved, which included 70% of patients with autoimmune urticaria and 43% with chronic idiopathic urticaria. Mean time to complete control was 14 weeks, with a range of less than 1 to 31 weeks. The dose of mycophenolate mofetil at complete control ranged from 1000 to 6000 mg divided twice daily. Mycophenolate mofetil was tapered in 7 of these 10 patients after an average of 7 weeks. Six of the 7 patients tapered then discontinued mycophenolate mofetil with remissions lasting between 2 and 16 weeks up to when the chart review ended. Mycophenolate mofetil was well tolerated with no serious infections or laboratory abnormalities. Gastrointestinal symptoms were most common. LIMITATIONS: This was a retrospective chart analysis. The number of patients was relatively small. CONCLUSIONS: Mycophenolate mofetil is a useful and well-tolerated second-line therapy for patients with autoimmune and chronic idiopathic urticaria in whom antihistamines and other therapeutic agents have failed.

Normal minimal erythema dose responses in patients with suspected photosensitivity disorders.

PURPOSE: Our study identified the most common diagnoses in patients with a history of photosensitivity or with a photodistributed eruption and normal minimal erythema dose (MED) responses. METHODS: We retrospectively reviewed the diagnoses and phototest results of 319 patients who were phototested at the New York University Photomedicine Section of the Charles C. Harris Skin and Cancer Pavilion from 1993 to 2009. Patients were phototested if they had a history of photosensitivity or had an eruption with a distribution that suggested photosensitivity. RESULTS: The majority of patients with normal MEDs were diagnosed with polymorphous light eruption, followed by contact or photocontact dermatitis, photodistributed dermatitis not otherwise specified (idiopathic), solar urticaria and photoexacerbated atopic dermatitis. DISCUSSION: The clinical history of photosensitivity and physical findings remain as important metrics in the diagnosis of patients with photodistributed dermatoses and normal MEDs.

Perifollicular Langerhans cell histiocytosis.

A 25-year-old man presented with a 13-year history of an erythematous, papular eruption of his face and trunk, which was treated in the past as acne and psoriasis with isotretinoin and methotrexate, respectively. Histopathologic examination demonstrated an infiltrate of Langerhans cells, which was consistent with Langerhans cell histiocytosis. The epidemiology, clinical presentation, and treatment options of this disease are reviewed.

A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis.

BACKGROUND: Retrospective chart reviews are periodically needed to update allergen series to detect changes in photoallergic contact dermatitis (PACD) over time. OBJECTIVE: We sought to evaluate photopatch test results during a 13-year period and extend the observations to 20 years. METHODS: A retrospective chart review was conducted in patients who were photopatch tested. RESULTS: In all, 76 patients were evaluated. A total of 69 positive photopatch and 45 positive patch test reactions were detected in 30 and 23 patients, respectively. The frequencies of the positive photopatch test reactions were sunscreens 23.2%, antimicrobial agents 23.2%, medications 20.3%, fragrances 13%, plants and plant derivatives 11.6%, and pesticides 8.7%. Of the positive photopatch reactions to antimicrobial agents, 60% were caused by Fentichlor. LIMITATIONS: This study was a retrospective chart analysis, and the number of patients was small. CONCLUSIONS: Sunscreens and antimicrobial agents were the most frequent allergens eliciting PACD, and there was a decrease in PACD caused by fragrances. The number of reactions to medications increased. This study also demonstrated that pesticides can be a cause of PACD. The detection of reactions to Fentichlor was unexpected and, although they have been attributed in some studies to cross-reactions to sulfanilamides and bithionol, such a robust association was not observed in this study. This study extends our experience of the changes in the allergens that elicit PACD to 20 years.