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.

[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.

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.

[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.

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.

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.

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.