Type I and Type IV allergy to unfractionated heparin and low-molecular-weight heparin with no reaction to recombinant hirudin

Aim:  To investigate the risk of adult hand eczema and possible influence on later working life in persons with childhood atopic dermatitis.
Method:  After reviewing medical records from the school healthcare in Stockholm regarding individuals born 1960–69, 600 individuals where signs of atopic dermatitis were noted ("cases") and 600 matched controls without eczema or allergic disease ("controls") were identified. 405 cases and 378 controls answered a questionnaire regarding past and present skin disease, choice of job, exposure at work and possible change of job due to eczema.
Results: Hand eczema was more than 3 times more common among cases, 42%, compared to controls, 13%(p < 0.001). Hand eczema during the past 12 months was reported by 24% of the cases and 9% of the controls (p < 0.001). The proportion of individuals working in jobs with high‐risk for hand eczema was equal between the groups, as well as exposure to water, detergents, chemicals and hand washing. Among the cases 9% reported change of job due to eczema compared to 2% of controls (p < 0.001) and sick leave 10% compared to 2%(p < 0.001).
Conclusions: Childhood atopic dermatitis is a risk factor for hand eczema. As the proportion of individuals in jobs with high‐risk for hand eczema and the exposure was the same in cases and controls measures preventive measures are important to reduce consequences like sick leave and change of job.     

Delayed-type hypersensitivity skin reactions caused by subcutaneous unfractionated and low-molecular-weight heparins: tolerance of a new recombinant hirudin

BACKGROUND: Eczema-like infiltrated plaques at subcutaneous heparin injection sites are well-documented side effects of these anticoagulants. However, surgical interventions may be problematic if heparin is urgently needed in these patients. OBJECTIVE: The aims of this study were to perform extensive allergy skin testing in 24 patients, including a pregnant woman in whom subcutaneous infiltrated plaques developed after subcutaneous heparin injections, and to find safe therapeutic alternatives for this group of patients. METHODS: Patch, intradermal, and subcutaneous tests were performed with a panel of unfractionated heparins (UFHs), low-molecular-weight heparins (LMWHs), and heparinoids. Since 1997, we have also been performing allergy studies in 8 patients with lepirudin, a new recombinant heparinoid; tolerance of lepirudin was investigated by means of subcutaneous and intravenous injections. The allergy investigations in the pregnant woman were limited to patch tests with heparins and intradermal and subcutaneous tests with pentosanpolysulfate, which are not contraindicated during pregnancy. RESULTS: In our study population 19 of 23 patients were sensitized to all the UFHs and LMWHs tested when intracutaneous and subcutaneous test results were read at up to 96 hours. LMWH was found to be a possible substitute in 4 patients. Five patients were also sensitized to the heparinoid pentosanpolysulfate. Sensitization to the heparinoid danaparoid was observed in 12 of the 13 patients who were tested with this substance. The administration of an intravenous bolus containing a therapeutic dose of lepirudin after negative subcutaneous provocation was tolerated without any side effects in all 8 patients. The pregnant woman was sensitized to LMWH but tolerated subcutaneous pentosanpolysulfate without any side effects. CONCLUSION: Extensive allergy skin testing should be performed to find safe alternatives. With few exceptions, all patients react to both UFHs and LMWHs, as well as to danaparoid. The subcutaneous provocation test is the most reliable diagnostic measure. Intravenous lepirudin, and in some cases subcutaneous pentosanpolysulfate, appears to be a safe alternative in patients with eczema-like infiltrated plaques at subcutaneous heparin-injection sites.     

Arthus reaction to lepirudin, a new recombinant hirudin, and delayed-type hypersensitivity to several heparins and heparinoids, with tolerance to its intravenous administration

The pathogenesis of allergic reactions to heparin is poorly understood. Clinically, this phenomenon is relevant because of its increasing incidence and the resulting therapeutic challenges due to various cross-reactions between unfractionated and low-molecular weight heparins as well as between heparins and heparinoids. A 44-year-old female patient had developed a delayed-type hypersensitivity to certoparin-sodium. Diagnostic allergy testing revealed various cross-reactions between different heparins as well as an intolerance to heparinoids. After subcutaneous challenge with the recombinant hirudin lepirudin (Refludan) the patient developed a local Arthus reaction at the injection site. In general, recombinant hirudins do not cross-react with high- or low-molecular weight heparins and heparinoids because of a different molecular structure and are therefore an alternative in case of adverse reactions to heparins and heparinoids. Whereas a local Arthus reaction has already been described twice for low-molecular weight heparins, this is to the best of our knowledge the first observation of a superficial leukocytoclastic vasculitis due to s.c. applied lepirudin. Intravenous administration of heparins and heparinoids in case of hypersensitivity to these drugs following topical application risks a generalized eczematous reaction in patients with delayed-type allergy to both groups of substances. In our patient with delayed-type hypersensitivity to heparins and heparinoids and superficial vasculitis due to lepirudin, the intravenous challenge with heparin and a heparinoid was justified as an ultima ratio measure and proved to be the useful therapeutical alternative.     

New fillers for the new man

ABSTRACT:  Two new collagen-based lidocaine-containing dermal fillers, ArteSense™/ArteFill™ (Artes Medical, San Diego, CA) and Evolence® (Colbar LifeScience Ltd., Herzliya, Israel), have proved to be of particular interest to men, many of whom seek a long-lasting or permanent correction. ArteFill™ has been available in the United States since 2006, and it is expected that Evolence® will reach the American market in 2008. The properties of the two products will be described, and experience based on the administration of many hundreds of syringes of both products by a Canadian dermatologist will be detailed here, with tips and precautions to optimize patient outcomes.     

Outcomes and adverse effects of ablative vs nonablative lasers for skin resurfacing: A systematic review of 1093 patients

It is generally believed that ablative laser therapies result in prolonged healing and greater adverse events when compared with nonablative lasers for skin resurfacing. To evaluate the efficacy of ablative laser use for skin resurfacing and adverse events as a consequence of treatment in comparison to other modalities, a PRISMA‐compliant systematic review (Systematic Review Registration Number: 204016) of twelve electronic databases was conducted for the terms “ablative laser” and “skin resurfacing” from March 2002 until July 2020. Studies included meta‐analyses, randomized control trials, cohort studies, and case reports to facilitate evaluation of the data. All articles were evaluated for bias. The search strategy produced 34 studies. Of 1093 patients included in the studies of interest, adverse events were reported in a total of 106 patients (9.7%). Higher rates of adverse events were described in nonablative therapies (12.2% ± 2.19%, 31 events) when compared with ablative therapy (8.28% ± 2.46%, 81 events). 147 patients (13.4%) reported no side effects, 68 (6.22%) reported expected, transient self‐resolving events, and five (0.046%) presented with hypertrophic scarring. Excluding transient events, ablative lasers had fewer complications overall when compared with nonablative lasers (2.56% ± 2.19% vs 7.48% ± 3.29%). This systematic review suggests ablative laser use for skin resurfacing is a safe and effective modality to treat a range of pathologies from photodamage and acne scars to hidradenitis suppurativa and posttraumatic scarring from basal cell carcinoma excision. Further studies are needed, but these results suggest that ablative lasers are a superior, safe, and effective modality to treat damaged skin.     

Genetic alterations in RAS‐regulated pathway in acral lentiginous melanoma

Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS‐related pathways are present in 87.5% of acral lentiginous melanomas.     

Self‐resolving superficial primary cutaneous mucormycosis in a 7‐week‐old infant

A 7‐week‐old girl, born at 30 weeks' gestational age, presented to clinic for evaluation of a crop of vesicular lesions that were noted after removal of a bandage that had been in place for 4 days. A punch biopsy of the lesion revealed fungal elements that were later identified as Rhizopus spp. The lesion began to self‐resolve, and no further treatment was needed, with full resolution of the lesion by 1 month after presentation. Clinicians should be aware of the variable presentations of mucormycosis and consider fungal infection in the differential diagnosis when evaluating vulnerable patients with skin eruptions.     

Pathogenic role of IL-17 in psoriasis and psoriatic arthritis

Psoriasis is a chronic inflammatory skin disorder resulting from a complex network of cytokines and chemokines produced by various immune cell types and tissue cells. Emerging evidence suggests a central role of IL-17 and IL-23/T17 axis in the pathogenesis of psoriasis, giving a rationale for using IL-17-blocking agents as therapeutics.Three agents targeting IL-17 signaling are being studied in Phase III clinical trials: secukinumab and ixekizumab (IL-17 neutralizing agents), and brodalumab (IL-17 receptor antagonist). Preliminary results are highly promising for all anti-IL17 agents, creating fair expectations on this class of agents as the new effective therapeutic approach for the treatment of psoriasis.     

Combined effects of irritants and allergens. Synergistic effects of nickel and sodium lauryl sulfate in nickel- sensitized individuals

Knowledge of the combined effects of irritants and allergens is of interest with respect to accurate risk assessment. The threshold for elicitation of allergic contact dermatitis in previously sensitized individuals may theoretically be markedly influenced by the simultaneous presence of irritants and allergens. Combined exposures have, however, only been studied infrequently. In the present study, the combined effect of an irritant and an allergen was evaluated in a dose-response designed experimental study. 20 nickel-sensitized subjects were exposed to patch testing with varying concentrations of NiCl2 (nickel chloride) and sodium lauryl sulfate (SLS) alone and in combination. Evaluation of skin reactions was performed by colorimetry, measurement of transepidermal water loss and clinical evaluation, and the data were analyzed by logistic dose-response models. A synergistic effect was found of combined exposure to NiCl2 and SLS, as compared to each of the substances applied separately, as evaluated by colorimetry and clinical scoring. This means that the effect produced by the combined exposure was substantially greater than the effect produced by either of the substances alone. A synergistic effect of combined exposure on skin barrier impairment was not found, since the barrier function is significantly influenced by SLS-exposure only and not by NiCl2. Concentration limits are used by industry and government agencies to protect consumers. The present results clearly illustrate that elicitation thresholds and concentration limits may be influenced considerably by combined exposure to allergens and irritants.     

Compound heterozygous mutations in desmoplakin associated with skin fragility,follicular hyperkeratosis,alopecia, and nail dystrophy

Desmoplakin mutations are associated with a wide variety of phenotypes affecting the skin, nails, hair, and heart. A 21‐month‐old boy was born with multiple erosions resembling epidermolysis bullosa, complete alopecia, nail dystrophy, palmoplantar keratoderma, and areas of follicular hyperkeratosis. He was found to have two heterozygous mutations in the desmoplakin gene: c.478 C>T in exon 4 (p.Arg160X) and c.3630T>A in exon 23 (Tyr1210X). This case expands the clinical spectrum associated with desmoplakin mutations and highlights a mutation in exon 23 that has not been previously reported in the literature.     

Evidence‐based skin care in preterm infants

Most guidelines on neonatal skin care emphasize issues pertaining to healthy, term infants. Few address the complex task of skin barrier maintenance in preterm, very preterm, and extremely preterm infants. Here, we provide an evidence‐based review of the literature on skin care of preterm neonates. Interestingly, the stratum corneum does not fully develop until late in the third trimester, and as such, the barrier function of preterm skin is significantly compromised. Numerous interventions are available to augment the weak skin barrier of neonates. Plastic wraps reduce the incidence of hypothermia while semipermeable and transparent adhesive dressings improve skin quality and decrease the incidence of electrolyte abnormalities. Tub bathing causes less body temperature variability than sponge bathing and can be performed as infrequently as once every four days without increasing bacterial colonization of the skin. Topical emollients, particularly sunflower seed oil, appear to reduce the incidence of skin infections in premature neonates—but only in developing countries. In developed countries, studies indicate that topical petrolatum ointment increases the risk of candidemia and coagulase‐negative Staphylococcus infection in the preterm population, perhaps by creating a milieu similar to occlusive dressings. For preterm infants with catheters, povidone‐iodine and chlorhexidine are comparably effective at preventing catheter colonization. Further studies are necessary to examine the safety and efficacy of various skin care interventions in premature infants with an emphasis placed on subclassifying the patient population. In the interim, it may be beneficial to develop guidelines based on the current body of evidence.     

Untersuchung der Kompatibilität verschiedener dermatologischer Rezepturen mit Kompressionsgestricken

Summary: Skin care is essential for many patients wearing compression hosiery. However, skin care products may impact the elasticity of the stockings. Since a recommendation of skin care products would be of great value for the patients we have developed a method for testing the influence of creams and lotions on compression hosiery. Stockings manufactured from synthetic yarns are almost resistant towards the effects of the analyzed formulations while fabric containing natural rubber is heavily influenced by most of these products. Besides Paraffinum liquidum other ingredients have a negative impact on the elastic properties of natural rubber. With the help of this method we are able to select dermatological preparations which can be used without harming the delicate fabric of compression hosiery.     

Occupational allergic contact dermatitis from spices

About 1000 patients were investigated at our clinic during 1991 for occupational skin disease. and 5 had occupational allergic contact dermatitis from spices. The patients were chefs, or kitchen, coffee room, and restaurant workers. All patients had hand (or finger) dermatitis. The causative spices were: garlic, cinnamon, ginger, allspice and clove, The same patients also had allergic patch test reactions to foods: tomato, lettuce and carrot. Paprika elicited a weak allergic patch test reaction in 2 patients. Occupational allergic contact dermatitis from spices is relatively rare, but needs to be taken into consideration in patients who have hand dermatitis, and work with spices and foods, Patch testing with spices as is useful, but testing with dilutions in pet, may be needed to confirm that the patch test reactions are allergic. Patients also need to be prick tested with spices and foods.