Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial.

BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.

Medical, psychological and socio-economic implications of chronic hand eczema: a cross-sectional study.

BACKGROUND: Hand eczema (HE) is a common skin disease with major medical psychological and socio-economic implications. Onset and prognosis of HE are determined by individual as well as environmental factors. So far, most epidemiological data on HE have been reported from Scandinavian and recently German studies. OBJECTIVE: To investigate the characteristics and medical care of patients with chronic HE (CHE) in Switzerland, and identify risk factors. METHODS: In this cross-sectional study, data from patients with chronic HE were obtained by means of medical history, dermatological examination and patient questionnaires. Multiple logistic regression analysis was applied to identify risk factors for high severity and dermatology life quality index (DLQI). RESULTS: In seven dermatology departments, 199 patients (mean age 40.4 years, 50.8% female) with CHE (mean duration 6.6 years) were enrolled. Moderate to severe HE was reported by 70.9% of patients, and was associated with age <30 or >50 years, localization of lesions and pruritus. Because of the CHE, 37.3% of patients were on sick leave over the past 12 months, 14.8% had changed or lost their job. Practically all patients applied topical therapy, 21% were treated with alitretinoin, and 21% with psoralen plus UVA light (PUVA). The effects on the health-related quality of life was moderate to large in 33.7% and 39.4% of CHE patients, respectively. Factors associated with a high impact on DLQI (mean 9.7 ± 5.8) were female sex, lesions on back of the hands and pruritus as well as mechanical skin irritation and wearing gloves. CONCLUSION: In agreement with recent studies, the Swiss data demonstrate the high impact of CHE on medical well-being, patient quality of life and work ability. As it is associated with an intense use of health care services, high rate of sick leave, job loss and change, CHE may cause a high socio-economic burden.

Is drug allergy less prevalent than previously assumed? A 5-year analysis.

BACKGROUND: Rashes are a frequent conundrum in clinical practice as they may be reactive, drug induced or disease specific. Identification of the culprit drug is important as re-exposure may be harmful or even life-threatening and unnecessary avoidance of 'innocent' drugs leads to limitations of treatment options. OBJECTIVE: To objectify the cause of suspected cutaneous drug reactions in a large patient population. METHOD: Over 5years (2006-10), 612 patients with suspected cutaneous drug reactions were evaluated. Histology was assessed. About 200 patients were invited for complete work-up with skin tests (prick/intracutaneous testing and scratch/patch as indicated) and, if necessary, lymphocyte transformation tests (LTT). In special cases, drug provocation tests were conducted. RESULTS: A total number of 141 cases with suspected drug reaction underwent full work-up (age 6-86years; 75% female, 25% male). In 107 cases (76%) a drug was identified whereas 34 (24%) were reactive rashes or had other causes. Mostly, cutaneous drug reactions were maculopapular rashes, urticaria/angio-oedema; less frequently, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, systemic drug-related intertriginous and flexural exanthema, toxic epidermal necrolysis and fixed drug eruptions were present. Of all the cutaneous drug reactions investigated, 39·8% were caused by antibiotics, 21·2% by anti-inflammatories, 7·6% by contrast media and 31·4% by others (oral antidiabetics, antimycotics, antipsychotics, antiepileptics and others). CONCLUSION: Clinical assessment overestimates the role of drug allergies in cutaneous reactions. Assessment of suspected drug reactions can be greatly improved by thorough evaluation including dermatological and allergological work-up with skin testing and assays such as LTT.

Contact dermatitis induced by glatiramer acetate.

Glatiramer acetate (Copaxone(®)) is an immunomodulatory polypeptide used in patients with relapsing-remitting multiple sclerosis. It represents a safe treatment option with mild side effects. In this study, we look at a 39-year-old woman who received glatiramer acetate as subcutaneous injections for two months and developed contact dermatitis. The drug had to be stopped, and treatment with topical prednisone was initiated. Prick/scratch testing was negative but the lymphocyte transformation test was highly positive for glatiramer acetate. This is the first report on contact dermatitis induced by glatiramer acetate injections. The treatment consisted of local topical steroids and cessation of the drug.

[Swiss clinical practice guidelines for skin cancer in organ transplant recipients]. / Recommandations suisses pour la prise en charge des cancers cutanés chez les patients transplantés d'organe.

Swiss clinical practice guidelines for skin cancer in organ transplant recipients Transplant patients have increased over the last decades. As a consequence of long-term immunosuppression, skin cancer, in particular squamous cell carcinoma (SCC), has become an important problem. Screening and education of potential organ transplant recipients (OTRs) regarding prevention of sun damage and early recognition of skin cancer are important before transplantation. Once transplanted, OTRs should be seen yearly by a dermatologist to ensure compliance with sun avoidance as well as for treatment of precancerosis and SCC. Early removal is the best treatment for SCC. Reduction of immunosuppression, switch to mTOR inhibitors and chemoprevention with acitretin may reduce the incidence of SCC. The dermatological follow-up of OTRs should be integrated into a comprehensive post-transplant management strategy.

Swiss clinical practice guidelines for skin cancer in organ transplant recipients.

Patients with a solid organ transplant have increased in numbers and in individual survival in Switzerland over the last decades. As a consequence of long-term immunosuppression, skin cancer in solid organ recipients (SOTRs) has been recognized as an important problem. Screening and education of potential SOTRs about prevention of sun damage and early recognition of skin cancer are important before transplantation. Once transplanted, SOTRs should be seen by a dermatologist yearly for repeat education as well as early diagnosis, prevention and treatment of skin cancer. Squamous cell carcinoma of the skin (SCC) is the most frequent cancer in the setting of long-term immunosuppression. Sun protection by behaviour, clothing and daily sun screen application is the most effective prevention. Cumulative sun damage results in field cancerisation with numerous in-situ SCC such as actinic keratosis and Bowen's disease which should be treated proactively. Invasive SCC is cured by complete surgical excision. Early removal is the best precaution against potential metastases of SCC. Reduction of immunosuppression and switch to mTOR inhibitors and potentially, mycophenolate, may reduce the incidence of further SCC. Chemoprevention with the retinoid acitretin reduces the recurrence rate of SCC. The dermatological follow-up of SOTRs should be integrated into the comprehensive post-transplant care.

Familial cutaneous mycosis fungoides: successful treatment with a combination of gemcitabine and alemtuzumab.

We report a familial cutaneous T-cell lymphoma in father and son. After different treatment modalities without lasting responses, the son was treated with gemcitabine as single agent and due to insufficient effect with alemtuzumab monotherapy. Only after the two drugs had been combined did we observe a remarkable response of the skin lesions and disappearance of enlarged lymph nodes. The combined treatment with gemcitabine and alemtuzumab was well tolerated, and no increased toxicity was noted. The combination of these two active agents may provide an additional option in the treatment of cutaneous T-cell lymphoma.

[Herpetic folliculitis barbae. A rare cause of folliculitis]. / Die herpetische Folliculitis barbae. Eine seltene Ursache einer Follikulitis.

Viral folliculitis is a rare disease usually caused by herpes simplex, herpes zoster and molluscum contagiosum in immune-compromised patients. An otherwise healthy 30 year old patient without history of herpes simplex contracted a folliculitis in the beard region after a flu-like illness. He had no oral or labial lesions but instead showed a crusty erythematous folliculitis confined to the beard region with small grouped vesicles on the neck and reactive cervical lymph nodes. Bacterial and mycological analysis from swabs were negative. The culture was positive for herpes simplex virus and the immune fluorescence showed HSV type 1. Systemic therapy with valaciclovir 2x 500 mg/d and lotio alba locally led to rapid improvement. When confronted with folliculitis, non-bacterial causes such as viral (herpes simplex, herpes zoster, molluscum contagiosum), mycological (pityrosporon, candida), demodex and eosinophilic follicultitis should be taken under consideration.

Allergens in celery and zucchini.

The aim of this study was to confirm allergy to celery tuber and to zucchini, for the first time, by DBPCFC, and to identify the allergens recognized by IgE from DBPCFC-positive patients. Therefore, raw vegetables were hidden in a broccoli drink, and a DBPCFC-procedure was developed that consisted of a spit and swallow protocol, making sure that the procedure was safe for the patients and that reactions strictly localized to the oral cavity as well as systemic reactions could be reproduced by DBPCFC. The allergens in celery and zucchini extract were identified by immunoblot inhibition using allergen extracts, recombinant allergens and purified N-glycans as inhibitors. Celery allergy was confirmed in 69% (22/32) of subjects with a positive case history. Four subjects with a history of allergic reactions to zucchini had a positive DBPCFC to this vegetable. During DBPCFC, systemic reactions were provoked in 50% (11/22) of the patients to celery, and in 3/4 of the zucchini-allergic patients. The Bet v 1-related major celery allergen was detected by IgE of 59% (13/22) of the patients. Cross-reactive carbohydrate epitopes (CCD) bound IgE of 55% (12/22) of the celery-allergic patients and in 2/4 of the subjects with zucchini allergy. Profilin was a food allergen in celery in 23% (5/22) and in zucchini in 2/4 of the cases. A zucchini-specific allergen was detected by IgE from one patient. We conclude that ubiquitous cross-reactive structures are important in allergy to both, celery and zucchini, and that a specific association to birch pollen allergy exists in allergy to celery (mediated by Api g 1), but not in zucchini allergy.

Allergy caused by ingestion of persimmon (Diospyros kaki): detection of specific IgE and cross-reactivity to profilin and carbohydrate determinants.

BACKGROUND: Allergy to persimmon (Diospyros kaki) is very rare and not yet confirmed by means of double-blind, placebo-controlled, food-challenge (DBPCFC). Thus far, specific IgE to this fruit and cross-reactivity to pollen and other foods has not been determined. OBJECTIVE: The objective was to confirm allergy to persimmon in 3 patients with an according personal history and to characterize allergens and cross-reactivity of specific IgE antibodies to pollen and food allergens. One patient reacted with pruritus, penis edema, urticaria, and asthma; the second reacted with nausea and vomitus; and the third reacted with rhinoconjunctivitis, asthma, and stomachache after ingestion of persimmon. METHODS: Patients underwent skin prick testing with routine allergens, latex, persimmon, and other foods. Allergy to persimmon was confirmed by means of a DBPCFC. Specific serum IgE levels were measured with CAP-FEIA and the enzyme allergosorbent test (EAST) method. EAST and immunoblot inhibitions were carried out with persimmon; birch, grass, and ragweed pollen; latex; and N-glycans as inhibitors. RESULTS: All patients had positive skin test responses, DBPCFC and specific IgE assays to persimmon. Blot and EAST inhibition assays revealed IgE to cross-reactive profilin in one patient and IgE to cross-reacting carbohydrate determinants in all patients. CONCLUSIONS: This is the first report on 3 cases of allergy to persimmon verified by means of DBPCFC and detection of specific IgE. The sensitization is due to cross-reactive profilin and carbohydrate determinants.

[Ant venoms: a rare cause of allergic reactions in Switzerland]. / Ameisengift: eine seltene Ursache für allergische Reaktionen in der Schweiz.

In Switzerland, unlike other countries, allergic reactions to ants are a rare phenomenon when compared to the well known allergies to bee and wasp venom. In this report we present a series of case reports and a review of the different types of allergy to ants. Due to increased travel and heterogeneity of the population, we have observed several patients with sensitisation or allergy to the venom of imported fire ants (Solenopsis), a species of ant found in the Americas. Furthermore, allergic reactions to bites of the mound-building wood ant (Formica rufa), whose habitat is Central and Northern Europe, have been documented. Whereas reactions to fire ants can be life-threatening, reactions to mound-building wood ants have led to marked local reactions and in 2 cases to dyspnoea and wheezing. These reactions could be due either to primary sensitisation to ant venom or cross-reactivity in the presence of an allergy to wasp venom. Evaluation of patients presenting with a potential ant venom allergy includes a detailed personal history, skin testing and determination of specific IgE. However, to date only extracts from fire ants are commercially available for diagnostic tests. In the light of our observations we assume cross-reactivity between the venoms of fire ants and mound-building wood ants, and it therefore seems appropriate to use fire ant diagnostics in determining sensitisation to mound-building wood ants. In patients with severe fire ant-venom allergy we recommend desensitisation by immunotherapy, whereas in patients presenting with minor allergic reactions, e.g. after bites by mound-building wood ants, we provide the patients with emergency medication. Since current knowledge of ant allergies in Europe is limited, further studies are warranted.

Allergy caused by ingestion of zucchini (Cucurbita pepo): characterization of allergens and cross-reactivity to pollen and other foods.

BACKGROUND: Allergy to zucchini (Cucurbita pepo), a member of the Cucurbitaceae family, has not previously been reported. We examined 4 patients complaining of allergic symptoms, such as oral allergy syndrome, nausea, diarrhea, or pruritus, after the intake of zucchini. OBJECTIVE: After the confirmation of food allergy, we wanted to characterize zucchini allergens and examine possible cross-reactions to pollen and food. METHODS: The patients underwent skin prick and prick-to-prick-testing with different allergens, including zucchini, latex, and birch, ragweed, and grass pollen. Moreover a double-blind, placebo-controlled, food challenge was performed to confirm food allergy. Total and specific serum IgE levels were determined by using CAP-FEIA and the enzyme allergosorbent test method (EAST), respectively. Proteins from zucchini reacting with patient IgE were detected by means of immunoblotting. To characterize cross-reacting IgE antibodies, immunoblot- and EAST-inhibition assays were carried out. RESULTS: All patients in this study had positive reactions to zucchini both in prick-to-prick tests and double-blind, placebo-controlled, food challenges. Specific serum IgE levels to zucchini were found in all cases. In blot- and EAST-inhibition assays IgE from two patients revealed binding to zucchini profilin at about 15 kd. Furthermore, in two cases, including one of the profilin-positive patients, IgE directed against cross-reacting carbohydrate determinants was detected. For one patient, no cross-reacting IgE could be found, but IgE from this patient reacted strongly with a zucchini protein at 17 kd. CONCLUSIONS: We report the first 4 cases of food allergy to zucchini. Zucchini allergens can cause systemic reactions and are at least partially heat stable. We suggest that allergy to zucchini can occur as a result of primary sensitization to zucchini, as well as to cross-reactions to the panallergen profilin and cross-reacting carbohydrate determinants.

[Peanut anaphylaxis: the problem of hidden allergens]. / Anaphylaxie auf Erdnuss: das Problem versteckter Allergene.

HISTORY: Three patients developed recurrent anaphylactic reactions after ingestion of different kinds of food (Asian food, chocolate products, bakery products). INVESTIGATIONS: In all three patients a severe peanut allergy was confirmed either by skin prick testing or serologically (specific IgE for peanut of CAP class 3,4 and 6 respectively). Peanut allergy in all patients explained the anaphylactic reactions due to ingestion of hidden peanut in the food. TREATMENT: Patients were told to avoid the allergen. Because accidental ingestion is frequent in peanut allergy, they were equipped with a document stating the severity of the allergy and emergency medication (antihistamines, oral steroids, adrenaline injector). CONCLUSIONS: Peanuts can be concealed in different kinds of food because they are cheap, rich in protein and are often used to change the viscosity of other foods. Especially the American and Asian cuisines use peanuts in a wide variety of recipes. Furthermore accidental ingestion can occur due to false or lacking declaration of peanuts in processed food. Patients with peanut allergy should be informed about these possibilities.

Unilateral agminated angiofibromas: a segmental expression of tuberous sclerosis?

We present a case of acquired unilateral agminated angiofibromas in a 26-year-old patient with onset at the age of 18. He developed over 100 pigmented dome-shaped papules on the left side of his nose, cheek and chin. Histological examination showed acanthosis and dermal capillary proliferations, fibrosis and lymphohistiocytic infiltrates. Staining with CD-31 showed increased vascular formation in the dermis. Staining for S-100 protein, HMB-45, NKIC-3 and Masson-Fontana staining showed no nevocytes or melanocytes in the dermal tissue, suggesting that the lesions are a segmental expression of tuberous sclerosis. However, multiple agminated angiofibroma without a relationship to tuberous sclerosis or a nevocytic or melanocytic formation cannot be ruled out for certain.

Subtraction procedure for the registration of tissue perfusion with Doppler ultrasound.

Tissue perfusion, i.e., in muscles or parenchymatous organs, is of both physiological and pathophysiological interest. The measurement of tissue perfusion is an unsolved problem. The Doppler ultrasound method is well suited to this purpose. However, measurements using this technique may be disturbed by movements or vibrations such as heart motion, muscle trembling or vibration of the subsoil (i.e. the examination table). These interfering movements produce Doppler frequencies in the same frequency range as slowly flowing erythrocytes, causing artifacts to appear in the measured data. The goal of this project was to suppress such artifacts with the help of a subtraction procedure. The mathematical theory of this subtraction procedure and its implementation in a newly developed two channel Doppler system are presented. This system was successfully tested on a phantom which is able to generate flow and movement artifacts. Preliminary measurements in the forearms of volunteers showed that movement artifacts can be at least partially suppressed.