Does frequency of genital herpes recurrences predict risk of transmission? Further analysis of the valacyclovir transmission study

BACKGROUND: The benefit of suppressive antiviral therapy for reducing the risk of herpes simplex virus (HSV)-2 transmission to sex partners may be enhanced if persons at high risk for transmission can be identified. OBJECTIVE: To determine whether frequency of genital herpes recurrences is associated with increased risk of HSV-2 transmission. METHODS: Analysis of recurrence frequency and shedding frequency (subset) among participants in a randomized controlled trial of valacyclovir 500 mg qd versus placebo for reducing the risk of HSV-2 transmission. RESULTS: Overall, 1484 monogamous HSV-2-serodiscordant couples participated and 41 HSV-2 transmissions occurred during the 8-month trial; 40 were able to provide a history of recurrence frequency. The rate of recurrences per year before study entry did not differ between source partners who transmitted and those who did not, 4.8 versus 5.1, respectively. Similarly, the mean frequency of recurrences observed during the study also did not differ among those who transmitted versus those who did not for placebo recipients (4.4 vs. 4.8) or valacyclovir recipients (1.4 vs. 1.3). Among the 40 source partners who transmitted HSV-2, 8 of 27 placebo recipients and 7 of 13 valacyclovir recipients had no recurrences during the study. CONCLUSION: Clinical assessment of HSV-2 disease severity as defined by the frequency of genital herpes recurrences does not predict the risk of transmission to sexual partners. Though patients with frequent recurrences are most likely to benefit clinically from suppressive therapy, frequency of recurrences is not helpful in identifying persons who are most likely to transmit HSV-2.     

Can people affected by leprosy at risk of developing plantar ulcers be identified? A field study from central Ethiopia

In the ALERT leprosy control programme, 75 people affected by leprosy, in three different geographical areas, were investigated. Each person was documented as having anaesthesia to the 10 g monofilament. The study sought to determine why some people developed ulcers whilst others did not. According to the records, 43 had an ulcer during the last 5 years but 32 had never had an ulcer. In order to examine protective sensation on the sole of the foot, various sensory modalities were tested and the functional anatomy of the foot was examined. The results showed, as may be expected, that it is not possible to define a specific threshold for protective sensation that could be applied to all cases. Some people with only slightly diminished sensation developed ulcers, while many others with almost complete anaesthesia remained ulcer-free. In these rural communities, being a farmer reduced the risk of developing an ulcer, but no other demographic features were significant. Graded monofilaments were found to be the most appropriate test, with loss of sensation at any of five points tested being a 'positive' result. The 10 g filament was the most sensitive, but only 43% of feet identified by this test actually developed an ulcer. As people with partial loss of sensation were excluded from this study, this figure may be lower under programme conditions. The 50 g and 100 g filaments decrease the number of feet identified as at risk, but increase the percentage which actually develop an ulcer, to 46% and 49%, respectively. An appropriate test for selecting those for special programmes which may have a limited capacity, for example the provision of subsidized footwear or involvement in self-care groups, would be a 100 g filament, which would detect 86% of those feet likely to develop an ulcer, while reducing the number of those selected who are not at great risk. Vibrometry was found to be no better than graded filaments and an examination of functional anatomy did not help in identifying those at risk.     

Can the reporting of adverse skin reactions to cosmetics be improved? A prospective clinical study using a structured protocol

Background:  The use of cosmetics is rising, and adverse reactions to these products are increasing. In Sweden, the Medical Products Agency (MPA) keeps a voluntary reporting system for such adverse reactions. However, the reporting is sparse, consisting almost only of cases with test-proven allergic contact dermatitis, thus under-reporting the more common irritant reactions.
Objective:  The aim of the study was to try to improve the reporting system.
Patients and Methods:  Dermatologists at 3 dermatology departments used a structured protocol during the clinical investigation of 151 consecutive patients reporting skin reactions to cosmetics. The protocol included symptoms, signs, affected body site, suspected products, and final diagnosis after patch testing. Based on clinical data and patch test results, a causality assessment for each product was made according to a protocol used at the MPA.
Results:  Allergic contact dermatitis was found in 28% of the patients, and irritant reactions were equally common at 27%.
Conclusions:  Using this structured protocol, the cases of irritant dermatitis were also reported, and it is recommended that such a protocol is used as a standard to improve the reporting of adverse reactions to skin care products.     

Rash related to use of scented products. A questionnaire study in the Danish population. Is the problem increasing?

Fragrances are used in many types of cosmetic and household products, which are an important part of everyday life in modern society. The aim of the current investigation was to describe the frequency of self-reported rash due to scented products in a random sample of the adult Danish population. Further, it was determined whether risk of self-reported 1st-time rash from scented products had increased during the past 15 years compared to the preceding period. The sample consisted of 1537 persons, 801 female and 736 male, above the age of 15 years. The participants were interviewed person-to-person to obtain a general health profile, and in this connection, questions were asked concerning rash related to the use of scented products. 28.6% (440/1537) had on some occasion experienced rash from scented products, 10.6% had experienced rash within the year prior to interview. A multivariate analysis showed that women had a significantly increased risk of reporting rash from scented products compared to men (odds ratio: 1.56, p<0.0001). Furthermore, it was shown that individuals below the age of 40 years had a significantly increased risk of reporting rash from scented products compared to older age groups. The risk of reporting 1st-time rash occurring after 1978 was significantly increased (odds ratio: 2.34, p<0.0001), as compared to the preceding period. This may be taken as indicative of an increasing problem with scented products, involving potentially severe public health implications.     

Dysplastic naevi: To shave,or not to shave? A retrospective study of the use of the shave biopsy technique in the initial management of dysplastic naevi

The management of dysplastic naevi is a controversial subject. This study sought to assess the usefulness of the shave biopsy technique in the initial management of dysplastic naevi, and to demonstrate the advantages over the punch biopsy technique. We report a retrospective observational study of histopathology specimens examined in one histopathology practice over a 14-month period. Patients who had a clinical diagnosis of 'dysplastic naevus', which had initially been biopsied using either a shave or punch biopsy, and then followed up with a full-thickness elliptical excision, were included in the study. Histopathological concordance between the shave and punch biopsy specimens and their respective follow-up elliptical excisions was compared. We found that 21 of 22 (95.5%) shave biopsies were concordant with their respective excision specimens, and that 29 of 41 (70.7%) punch biopsies were concordant with their respective elliptical excision specimens. Of the shave biopsy specimens reviewed, 66% showed that the dysplastic naevi were completely excised with the initial biopsy, compared with 21.2% of the punch biopsy specimens. These findings confirm that shave biopsies provide accurate diagnostic information in the assessment of dysplastic naevi. Shave biopsies enable the entire lesion to be submitted for histopathological assessment, improving the chances of an accurate diagnosis.     

Can automated dermoscopy image analysis instruments provide added benefit for the dermatologist? A study comparing the results of three systems

BACKGROUND: Instruments designed to provide computer program-driven diagnosis of dermoscopic images of lesions are now commercially available. Multiple publications tout the improved diagnostic accuracy of these instruments compared with that of clinicians. OBJECTIVES: Our aim was to evaluate the actual usefulness of these instruments for dermatologists practising in a pigmented lesion clinic. METHODS: Over a 4-month period we subjected lesions, which were being evaluated in one of our clinics, to automated computer diagnosis performed by three commercially available instruments. We intentionally included three groups of lesions: group 1 lesions were suspicious melanocytic lesions that were scheduled to be excised; group 2 lesions were nonmelanocytic lesions; group 3 lesions were clinically obvious melanomas. The automated diagnoses provided by the instruments were compared with the dermoscopy diagnosis of experienced physicians and with histopathology. RESULTS: We included a total of 107 lesions. One imaging system's computer algorithm was unable to analyse one third of the lesions. All three instruments' computer algorithms were able to identify the clinically obvious melanomas (group 3) correctly. However, all three systems tended to overdiagnose by incorrectly classifying most seborrhoeic keratoses (group 2) as potential malignant lesions. Concerning the suspect melanocytic lesions (group 1), which are precisely the lesions for which a dermatologist would welcome a second opinion, we found significant variability in the diagnostic accuracy of the instruments tested. However, all three systems providing computer-assisted diagnosis had a tendency to overdiagnose benign melanocytic lesions as potential melanomas. CONCLUSIONS: Although the image analysis systems tested by us correctly identified the clinically obvious melanomas, they were not able to discriminate between most dysplastic naevi and early malignant melanoma. Thus, for the moment these computer-assisted diagnostic imaging machines provide little to no added benefit for the experienced dermatologist/dermoscopist.     

Could azathioprine be considered as a therapeutic alternative in the treatment of alopecia areata? A pilot study

Alopecia areata is an autoimmune disease resulting in partial or total nonscarring hair loss and the treatment of severe alopecia areata is difficult. The aim of this study was to evaluate the efficacy and safety of azathioprine as a systemic monotherapy for moderate to severe alopecia areata. A total of 20 patients [14 men (70%) and six women (30%)] with minimum 6 months history of alopecia areata were included. The extent of scalp hair regrowth during and after the completion of the 6 months treatment was evaluated by the Severity of Alopecia Tool (the SALT score). The daily drug intake was calculated as 2 mg/kg of body weight. Mean duration of current episode of scalp hair loss was 26.4 (26.4 ± 17) months. Mean regrowth percentage was 52.3% (52.3 ± 38.4). Mean hair loss percentage before treatment was 72.7% (72.7 ± 28.3) compared with 33.5% (33.5 ± 30.7) after 6 months of azathioprine treatment. This showed a highly significant statistical difference (Paired t‐test, CI 95% = 21.5–54.1). Mean hair loss score (S₀–S₅) before treatment was 3.9 (3.9 ± 1.6) and after 6 months of azathioprine treatment was 1.8 (1.8 ± 1.3). Assessment showed significant difference from baseline score (sign test, P < 0.0001). No significant statistical difference was observed with respect to gender before and after azathioprine treatment. Treatment with azathioprine as a systemic monotherapy clinically produces relevant improvement in moderate‐to‐severe alopecia areata. Generally azathioprine is a low‐cost and well‐tolerated drug and with controlled studies on larger number of patients, long‐term efficacy and safety of this treatment should be investigated.     

Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis? A double-blind, placebo controlled study

The study aimed to evaluate the effectiveness of metronidazole 0.75% gel in patients with mild and moderate seborrhoeic dermatitis. Sixty-seven patients with seborrhoeic dermatitis were enrolled. Cases were randomly treated with metronidazole 0.75% gel or placebo for four weeks and were additionally followed up for another four weeks. Patients were evaluated by scoring before the treatment, once a week during the treatment and twice after the cessation of the treatment within a 15-day interval. Furthermore, patient satisfaction and doctor global evaluation were done at the end of the treatment and of the study as well. In the metronidazole group 33 patients (median age: 26, total severity score: 15.0 +/- 11.0 (median +/- interquartile range) and in the placebo group 34 patients (median age: 26, total severity score: 13.0 +/- 7.5) were enrolled in the study. Three patients from the metronidazole group and four patients from the placebo group did not attend to follow-up visits. Erythema, scales, papule, pruritus and the total severity scores in both group decreased significantly during the treatment when compared with the basal levels (p < 0.05). There was no difference between the two groups in terms of efficacy (p > 0.05). Total severity scores were found as 7.33 +/- 1.08 and 6.43 +/- 0.93 in the metronidazole and placebo groups at the end of the treatment, respectively. After the cessation of the treatment, all scores had increased rapidly. Total severity scores were 10.40 +/- 1.54 and 11.20 +/- 1.53 in the metronidazole and placebo groups one month after the cessation of the treatment, respectively. Both metronidazole 0.75% gel and the placebo were well tolerated by the patients. In conclusion, in the treatment of seborrhoeic dermatitis, administration of metronidazole 0.75% gel is well tolerated but it is only as effective as placebo and the disease severity quickly returns to the basal levels after the cessation of treatment.     

Do we alter ultraviolet sensitivity in vivo with stratum corneum rehydration? A pilot study and review of the literature

BACKGROUND: Numerous therapeutic schemes recommend topical administration of emollients immediately prior to ultraviolet (UV) B therapy. The rationale behind the clinical improvement is a presumed enhancement of UV transmission through the epidermis. Originating from this clinical observation, there has been some concern as to whether a well-hydrated skin in general might be more susceptible to actinic damage. OBJECTIVES: To investigate whether rehydration of healthy skin causes an altered UVB sensitivity in vivo. METHODS: We determined minimal erythema doses (MEDs) and erythema sum scores (ESSs) after differential rehydration of the skin in 10 healthy volunteers. In each subject six UVB phototests were performed after pretreatment with five different emulsifying ointments (unguentum emulsificans and dilutions with 30, 50, 70 and 90% aqua purificans) plus a negative control. In vivo evaluation of stratum corneum hydration was performed by measurement of electrical capacitance. RESULTS: The results of this randomized, double-blind in vivo study indicated that rehydration of normal stratum corneum with the emulsifying ointments tested did not result in a significantly altered sensitivity to the erythematous effects of UVB irradiation (no significant differences in MED and ESS). Furthermore, there was no correlation between measured stratum corneum hydration and the erythema response of healthy skin. CONCLUSIONS: Although many schemes recommend the administration of emollients prior to UV therapy, there have also been calls for caution, as an uncritical application may interfere with such treatment. We showed that the emulsifying ointments tested exhibited no photoprotective potential and thus are suitable for the pretreatment of psoriasis prior to phototherapy. It has long been discussed whether the effects of emollient pretreatment on response to UV occur only in psoriatic skin or also in healthy skin. Our results indicated that stratum corneum rehydration did not result in a significantly increased erythema response of healthy skin to UVB exposure. With regard to the use of rehydrating cosmetics in everyday life, the outcome of our pilot study is reassuring, as we could not confirm with our experimental design that well-hydrated healthy skin is more prone to actinic damage.     

Are adverse skin reactions to cosmetics underestimated in the clinical assessment of contact dermatitis? A prospective study among 1075 patients attending Swedish patch test clinics

It is known that cosmetics and skin care products can cause adverse skin reactions. However, the frequency of adverse reactions reported to the Medical Product Agency (MPA) in Sweden is low. The purpose of the present study was to evaluate the occurrence of adverse skin reactions to cosmetics among patients referred for standard patch testing owing to suspected contact dermatitis in general, most frequently hand eczema. Consecutive patients at four patch test clinics in Sweden were invited to participate; 1075 were included. Of these, 47.3% (54.2% women and 30.8% men) reported current or previous adverse skin reactions to cosmetics and skin care products. This group showed significantly more positive patch test reactions, a higher prevalence of atopic dermatitis and the dermatitis was more frequently located in the face and neck region. Our results show that patients referred for standard patch testing have--or have had--a large proportion of self-reported adverse reactions to cosmetics or skin care products. We conclude that among patients with suspected contact dermatitis, adverse reactions to cosmetics can be a more important aetiological and/or complicating factor than is commonly acknowledged and that the reporting of such reactions to the MPA probably can be improved.     

Fondaparinux: a suitable alternative in cases of delayed‐type allergy to heparins and semisynthetic heparinoids? A study of 7 cases

Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood. Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their alpha- and beta-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.