Successful treatment of severe recalcitrant vernal keratoconjunctivitis and atopic dermatitis associated with elevated IgE levels with omalizumab.

We report the clinical case of an atopic patient with important manifestations impacting the quality of life at the cutaneous and ocular site. The condition resisted conventional treatments, and omalizumab had to be used to treat the disease successfully.

The transcriptome of hand eczema assessed by tape stripping.

BACKGROUND: No biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the gold standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin-tape strips for molecular investigations enable noninvasive investigations of HE. OBJECTIVE: By using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/morphological subtypes was investigated. METHODS: Thirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, nonlesional, and healthy skin. Total RNA was extracted and WTS was performed. RESULTS: The largest molecular difference of HE patients with and without AD was found in nonlesional skin areas and included a downregulation of CXCL8 for HE patients without AD. Differences between allergic and irritant contact dermatitis included epidermal biomarkers such as EPHA1. CONCLUSION: Skin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes.

Warts and all: Fingolimod and unusual HPV-associated lesions.

BACKGROUND: Fingolimod is used to reduce relapse rates in relapsing-remitting multiple sclerosis (MS). It is a sphingosine 1-phosphate (S1P) analogue having antagonistic effects on S1P receptors. Its immunosuppressive effect is due to reduced circulating lymphocyte numbers, and it may also be associated with impaired intrinsic cancer surveillance. Fingolimod side effects include increased rates and severity of viral infections particularly varicella zoster. METHODS: We present five cases of chronic and treatment refractory warts associated with fingolimod therapy. RESULTS: Each of the five cases presenting with chronic warts while receiving fingolimod therapy had prolonged periods of lymphopenia and improvements were seen following dose reduction or cessation of fingolimod. CONCLUSION: Cutaneous warts are associated with human papilloma virus (HPV) infection, suggesting an increased risk of other HPV-driven conditions such as cervical cancer following fingolimod administration. HPV viruses are responsible for approximately 90% of cervical cancers as well as a significant portion of anogenital cancers and have a high prevalence in sexually active adults. Given the reduced immune response to viral infections and potential impaired cancer surveillance in those receiving fingolimod, HPV vaccination and frequent assessment for the development of HPV-associated malignancies are recommended.

Occupational allergic contact dermatitis caused by antibiotics in healthcare workers - relationship with non-immediate drug eruptions.

BACKGROUND: Occupational allergic contact dermatitis (ACD) in healthcare workers (HCWs) is common, but systemic antibiotics are rarely reported as the cause. OBJECTIVES: Characterize occupational ACD by handling systemic antibiotics. METHOD: A retrospective analysis was performed of ACD caused by systemic antibiotics among HCWs patch tested between 2010 and 2016 with a series of systemic antibiotics. RESULTS: We studied 4 female nurses aged 28-47 years who developed ACD while working in surgical departments. They had eczema of the hands, and forearms or face, and 1 patient, who previously had exanthema caused by flucloxacillin, also developed a generalized rash following airborne exposure to systemic antibiotics. Patch tests showed positive reactions to ampicillin and cefazolin in 1 patient, to cefotaxime and ceftriaxone in 2 patients, and to several penicillins in another patient. Three patients also reacted to rubber allergens, fragrances, and/or preservatives. All patients admitted having direct and sporadic exposure to systemic antibiotic solutions. Avoidance resulted in a significant improvement of ACD, but 1 patient had to change job. CONCLUSIONS: Occupational ACD caused by ß-lactam antibiotics, particularly cephalosporins, is significant in HCWs. Cross-reactions between ß-lactams are similar to those described in non-immediate drug eruptions. A relationship between systemic delayed drug hypersensitivity and ACD, as observed in one case, suggests that patients should avoid future use of the antibiotic to which they are sensitized.

Immunologic Studies of Progesterone-Induced Neutrophilic Urticaria.

A 33-year-old woman presented with recurring pruritic, erythematous papules around the mouth and on the hands, of 1.5 years' duration. These flares typically began several days before her menstrual cycle and persisted for approximately 1 week. Physical examination revealed urticarial plaques on the neck. Due to the nature of the eruption, which corresponded with her menstrual cycle, a diagnosis of autoimmune progesterone urticaria was considered and workup pursued.

Inflamed skin predisposes to sensitization to less potent allergens.

BACKGROUND: Irritant dermatitis, caused by genetic barrier dysfunction in atopic dermatitis or wet work in hand dermatitis, induces innate immune response that might predispose to allergic contact sensitization to less potent sensitizers. OBJECTIVES: We sought to determine if positive patch test results to less potent allergens are more prevalent in patients with a history of childhood flexural dermatitis or current wet work. METHODS: We examined our database of patients presenting to a contact dermatitis clinic tested to potential contact allergens as indicated by their history. Allergens from our most recent standard were studied if they could be classified as weak, moderate, or strong sensitizers based on published data from the local lymph node assay. Patients were stratified by a history of childhood-onset flexural dermatitis as a proxy for atopic dermatitis and by occupation. RESULTS: History of childhood-onset dermatitis predisposed to contact allergy to weak sensitizers and wet work to medium-potency sensitizers. Neither predisposed to contact allergy from strong sensitizers. LIMITATIONS: Association cannot prove causation. CONCLUSIONS: We conclude that strong sensitizers do not require wet work or atopy to cause sensitization. Barrier defects associated with childhood eczema and wet work may promote sensitization to weak antigens.

Generalized linear IgA dermatosis with palmar involvement.

Linear IgA bullous dermatosis (LABD) is a sub-epidermal blistering disorder characterized by deposition of IgA along the basement membrane zone (BMZ) as detected by immunofluorescence microscopy. The diagnosis is made by clinicopathologic correlation with immunofluorescence confirmation. Differentiation from other bullous dermatoses is important because therapeutic measures differ. Prompt initiation of the appropriate therapies can have a major impact on outcomes. We present three cases with prominent palmar involvement to alert the clinician of this potential physical exam finding and to consider LABD in the right context.

A case of lichen planus pemphigoides with autoantibodies to the NC16a and C-terminal domains of BP180 and to desmoglein-1.

Lichen planus pemphigoides (LPP) is a rare autoimmune blistering disease that occurs in association with lichen planus (LP). This report describes a 59-year-old Japanese female patient with LPP. The patient first showed LP lesions on her hands, and subsequently developed bullae on her extremities and erosions of the oral mucosa. The patient's serum was positive for IgG autoantibodies against the BP180 NC16a domain, the BP180 C-terminal domain and desmoglein-1. However, a serum sampled one and a half years before the diagnosis of LPP was negative for autoantibodies against BP180 NC16a and BP180 C-terminal domains. These findings strongly suggest that the damage to the basal cells in the LP lesions exposed a sequestered antigen or formed neoantigens, leading to the production of pathogenic autoantibodies for LPP. Most of the previous cases of LPP have produced autoantibodies to the NC16a domain of BP180. This is the first case in which autoantibodies to the C-terminal domain of BP180 were detected. The oral mucosal symptoms in this case may have been caused by autoantibodies to the BP180 C-terminal domain.

The association of antiphospholipid antibodies with cardiopulmonary manifestations of systemic sclerosis.

OBJECTIVES: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. RESULTS: One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.

Disseminated Herpes Simplex Virus presenting as crusted papules on the palms and soles of an immunosuppressed patient.

Disseminated Herpes Simplex Virus (HSV) may occur in immunosuppressed patients, most commonly causing visceral organ involvement and rarely presenting solely with cutaneous lesions. We report an interesting case of disseminated HSV in a 77-year-old immunocompromised man, presenting as necrotic papules and pustules with no associated systemic involvement.

Erythema multiforme in a newborn associated with acute acquired cytomegalovirus infection.

Erythema multiforme is exceptional in newborns, and none of the few available reports has revealed a clear etiologic agent, not even herpes simplex virus. Immunocompetent patients rarely present with cutaneous cytomegalovirus involvement, and few cases of cytomegalovirus-associated erythema multiforme have been described, none of them in newborns. We report the first case of erythema multiforme in a newborn associated with cytomegalovirus infection.

Anti-neutrophil cytoplasmic antibody-positive neutrophilic dermatosis of the dorsal hands.

Neutrophilic dermatosis of the hands is a localized variant of Sweet syndrome (SS). It was first reported in 1995, and is an uncommon condition, with < 100 cases reported to date. The female preponderance, morphological and histological features, and response to treatment are similar to SS, but it differs in its distribution on the body. There may also be a lack of systemic features and inconsistent laboratory findings. Significantly, about half of all cases are associated with haematological problems, i.e. myelodysplasia and leukaemia. Other cases may be associated with ulcerative colitis or solid tumours. We describe a case of a 71-year-old man with neutrophilic dermatoses of the hands, who also had involvement of the lips. There was an associated rise in his anti-neutrophil cytoplasmic antibody level, which corresponded with the activity of the disease.

Contact angioedema and rhinoconjunctivitis caused by Dendrobaena species and Sarcophaga carnaria used as fishing bait.

The flesh fly Sarcophaga carnaria is commonly used as fishing bait. Immunoglobulin (Ig) E-mediated reactions caused by the handling of this bait have been reported. The earthworm Dendrobaena species is increasingly being used as fishing bait but there have been no reported cases of allergy to this species to date. We studied a 26-year-old amateur angler who presented rhinoconjunctivitis, urticaria, and angioedema on handling S carnaria. He started to use Dendrobaena species instead but developed the same symptoms. The aim of this study was to identify the allergens involved in the patient's clinical reactions. The study was performed using immunoglobulin (Ig) E immunoblotting and immunoblotting inhibition assays.The patient's serum detected allergens from Dendrobaena species (of an apparent molecular weight of approximately 150, 60, 37, 24, 21 and 19 kDa) and S. carnaria (approximately 70 kDa and a smear ranging from 50 to 40 kDa). The patient was diagnosed with allergy to both Dendrobaena species and 5 carnaria. This is the first case describing Dendrobaena species as an allergic agent.

Pediatric COVID toes and fingers.

The emergence of the coronavirus disease 2019 (COVID-19) worldwide pandemic has been associated with a new constellation of cutaneous features in children. Among the unusual dermatologic presentations are the so-called COVID toes, inflammatory nodules of the feet and toes, sometimes involving the hands and fingers. These lesions mimic acral pernio, the synonym being chilblains. Unlike adult patients with COVID toes, children are less likely to manifest symptomatic COVID-19. Although a few studies have found some linkage to COVID-19 through the serum IgA or IgG severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, other studies have no demonstrable linkage suggesting that barefoot children in cold weather develop such lesions. It appears that the chilblain-like lesions related to the period of the COVID-19 pandemic may reflect a brisk immune response portending a good prognosis and perhaps some form of innate immunity. The possible need to screen for coagulopathy is unclear, but this has been suggested in one report. Until we fully understand the pattern of immune response to COVID-19, questions may persist as to how disease manifestations are linked to SARS-CoV-2 exposures.

Update on medical and surgical gloves.

Occupational dermatitis to personal protective equipment (PPE), particularly to gloves, mainly occurs in healthcare workers. They are all irritant and/or allergic contact dermatitis (eczema and contact urticaria). Prolonged glove wearing by healthcare workers favours skin irritation of the hands and wrists. It is very important to consider characteristics and materials of gloves used in the medical field. Rubber additives are the main allergens in gloves. Latex or natural rubber remains by far the most frequent cause for occupational contact urticaria from gloves. The problem of prevention of infections risks in the health environment and the choice of medico-surgical gloves is described. In a surgical environment (in ORS), double gloving is recommended. Today, it appears as the best protection, even if in France it is far from being systematically used. Choosing the appropriate medical or surgical gloves requires having sufficient preliminary information on the assets, drawbacks and use limits of each of them. In cases of known contact allergic dermatitis, advice from dermatologists or allergologists is essential when it comes to suggesting substitution gloves.

Palm tissue displaying a polyclonal autoimmune response in patients affected by a new variant of endemic pemphigus foliaceus in Colombia, South America.

We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF). On physical examination, the palms and soles of El Bagre-EPF patients reveal an edematous texture and mild hyperkeratosis, in comparison with the non-glabrous skin of the patients where blisters, pustules or other lesions are commonly found. Based on the preceding observation, we tested the palms of 20 El Bagre-EPF cases and 20 controls from the endemic area for any pathological alterations in the samples by direct immunofluorescence (DIF). Our DIF demonstrated pathological deposits of fibrinogen and albumin, as well as IgG, IgA, IgM, IgD and C3c, at 1) the epidermal basement membrane zone; 2) around isolated areas in the epidermis, 3) within the dermal vessels and nerves, and 4) in areas surrounding dermal neurovascular structures and sweat glands. Specific markers for blood vessels, including 1) anti-intercellular adhesion molecule 1 (ICAM-1)/CD54, and 2) anti-junctional adhesion molecule (JAM-A); as well as specific markers for nerves, including 1) anti-glial fibrillary acidic protein (GFAP), and 2) anti-human neuron specific enolase (NSE) co-localized with the patients' autoantibodies. Although no blisters, ulcerations, pustules or erosions are clinically observed on the palms of El Bagre-EPF patients, our DIF detected distinct immunoreactivity in palm tissue. These alterations may contribute to the clinically edematous texture of the palms and the mild clinical hyperkeratosis found in most of these patients. We propose that normal glabrous skin and non-glabrous skin may be different with regard to the expression of selected molecules, which may vary in number, size or structural organization depending on their anatomical site. Our findings may also partially explain the hyperkeratotic palms that have been clinically well documented in the chronic phase of fogo selvagem i.e., endemic pemphigus foliaceus, in Brazil.

Sites of dermatitis in a patch test population: hand dermatitis is associated with polysensitization.

BACKGROUND: Sites of dermatitis in larger series of contact allergic patients are rarely reported. Increased risk of polysensitization has been linked only to stasis dermatitis and leg ulcers. However, a large proportion of polysensitized individuals may have dermatitis in other skin areas. OBJECTIVES: To examine the site of dermatitis at time of first appearance in contact allergic individuals with special focus on the distribution of dermatitis in polysensitized individuals and to examine if widespread dermatitis is more frequent in polysensitized than in single/double-sensitized patients. METHODS: A matched case-control study was carried out including 394 polysensitized and 726 single/double-sensitized patients who responded to a postal questionnaire. All subjects were recruited from a hospital patch test population. RESULTS: The hands were the most frequent and the anogenital region was the least frequent skin area affected with dermatitis. Dermatitis on the hands/wrists [odds ratio (OR) 1.58], in the armpits (OR 1.56) and on the back (OR 1.91) was positively associated with polysensitization. The hands were the only skin area with dermatitis which maintained the association to polysensitization in two subpopulations consisting of, respectively, individuals with and without atopic eczema. Dermatitis on the scalp was negatively associated with polysensitization (OR 0.66) primarily for individuals without atopic eczema. The dermatitis did not seem to be more widespread in polysensitized compared with single/double-sensitized patients. CONCLUSIONS: Special awareness in patients with hand dermatitis seems justified either to prevent development of multiple contact allergies or to document polysensitization as an aetiological factor.