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Adverse reaction to drugs in children, experiences with "spontaneous monitoring" in The Netherlands.

Drug use may be the cause of a wide variety of different symptoms and disorders in children and many different mechanisms may be involved. A number of situations in childhood may predispose to the development of adverse reactions. In the country-wide "voluntary reporting system" for drug monitoring in the Netherlands, only a small percentage of 4.5 of the case reports concern children (14 years and younger). The reported experiences show that adverse reactions which are important in adults, e.g. blood dyscrasia, erythema multiforme and liver injury, may also be encountered in children. The predominance of physics reactions (e.g. agitation, hallucinations) in suspected relationship with a variety of drugs (sympathicomimetics, anticholinergics, antihistamines, oxolamine) and neurological effects (e.g. dyskinesia in association with metoclopramide or domperidone) suggest that the nervous system in childhood is susceptible to side effects of drugs; further study on this subject seems to be needed. Clinical trials in children are limited because of ethical considerations; as a consequence post-marketing surveillance should pay special attention to this vulnerable group of patients. (Tab. 10, Ref. 23).

Adverse Drug Reaction Reporting Systems↗

Actinic reticuloid.

AR can be regarded as the most severe variant of the spectrum of chronic actinic dermatitis. The exact etiology is still unknown, but is probably multifactorial, involving contact allergic, photoallergenic, phototoxic, immunologic, and metabolic factors. A diagnosis of AR should only be made when the following criteria are present: (1) persistent infiltrated papules and plaques on light-exposed skin, often with extension to covered areas or generalized infiltrated erythroderma; (2) photosensitivity to a broad spectrum of wavelengths, including UV-B, UV-A, and part of the visible spectrum; and (3) on histologic examination, a dermal infiltrate with presence of atypical lymphoid cells. When one or two criteria are lacking, the more general term chronic actinic dermatitis should be preferred. The presence of a lymphoid infiltrate dominated by CD8+ cells seems to be useful as an additional marker for a diagnosis of AR. A CD8+ predominance in dermal infiltrates is exceptional and has been reported in clinically distinguished conditions such as graft-versus-host disease, lichen planus, erythema multiforme, and pityriasis lichenoides acuta, as well as chronica, and, finally, in mycosis fungoides. In erythrodermic patients, the presence of a CD8+ -dominated dermal infiltrate and, especially, a reversed CD4+ to CD8+ ratio in the peripheral blood are highly characteristic for a definite diagnosis of AR. It is not known why preferentially CD8+ lymphocytes occur in AR. Exposure to UV radiation can induce the presence of suppressor cells. In late lesions of polymorphic light eruption, there is also an increase of CD8+ cells as compared with early lesions, perhaps contributing to local suppression of the inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Autoimmune progesterone dermatitis.

Seven patients had autoimmune progesterone dermatitis. The morphological findings illustrate the polymorphous nature of the disease in which urticaria, erythema multiforme, and dyshidrosiform lesions were seen. Recurrence of the eruption five to ten days prior to the menses with spontaneous resolution following the menses was present in all cases. Intradermal skin testing to progesterone was done to confirm the diagnosis. Six of the seven patients has a history of use of artificial progestational hormones prior to the beginning of their eruption. It is postulated that the artificial progesterones may have been the trigger for the development of their autosensitivity. Treatment with conjugated estrogens resulted in remission of the disease in five of the seven cases reported.

Adult↗

Oral ulcerations.

Ulcerations are common occurrences in the mouth. Causes include physical trauma, radiation, chemical injury, and microbial infection (bacterial, viral, and fungal). Some ulcerations, such as recurrent aphthous stomatitis, Behçet's syndrome, and erythema multiforme, are of uncertain etiology, whereas others (eg, pemphigus, pemphigoid) are apparently of immunologic origin. Malignant neoplasms also may present as ulcerations. Because the natural history and treatment varies with the diagnosis, the practitioner should become familiar with the clinical appearance of the various types of ulcerations so that appropriate treatment can be instituted.

Bacterial Infections↗

[Oral manifestations of skin diseases].

There exists a multitude of systemic diseases which exhibit consequential oral manifestations. Dermatologic disorders frequently involve intraoral and perioral tissues which dental practitioners should be familiar with. A compilation of disorders including; bullous diseases (such as Pemphigus Vulgaris, Erythema Multiforme, Pemphigoid, Dermatitis Herpetiformis, Epidermolysis Bullosa, and Darier's disease), as well as non bullous diseases (such as Lichen Planus, Psoriasis, Lupus erythematosus, Scleroderma, and Perioral Dermatitis); and their oral manifestations are presented in order to facilitate their early diagnosis and subsequent treatment.

Darier Disease↗

[The Stevens-Johnson syndrome from maprotiline and propranolol?].

A wide variety of agents have been associated with erythema multiforme, particularly drugs and infectious agents. We describe a typical Stevens-Johnson's syndrome developing 15 days after initiation of propranolol and maprotiline therapy. Other etiologies have been excluded by appropriate investigations and the responsibility of each drug is discussed.

Adult↗

Adult linear IgA bullous dermatosis: a polymorphic disorder.

We report on two patients with unusual forms of adult linear IgA bullous dermatosis. One was a middle-aged woman who had targetoid lesions and bullae on her trunk and extremities. This patient first presented with lesions that clinically resembled erythema multiforme, but these evolved into a widespread eruption with bulging, elongated bullae. Examination of a biopsy specimen showed changes compatible with dermatitis herpetiformis and bullous pemphigoid. Findings on immunofluorescence studies showed deposition of linear IgA at the basement membrane zone. The second patient was an elderly woman with intensely pruritic vesicles whom we classified as having vesicular pemphigoid, until the linear IgA band on direct immunofluorescent test results became the predominant immunofluorescent finding. These cases are reported because of their unusual clinical presentations. The mechanism for the targetoid lesions in the first patient is discussed.

Aged↗

Non-specifically activated human peripheral blood mononuclear cells are cytotoxic for human keratinocytes in vitro.

Cultured human keratinocytes were lysed by activated PBMC in a 4-h 51Cr release assay. PBMC were activated by incubation with 50 U/ml of rIL-2 for 4 days. The cytotoxic precursors were found to be NKH1+ and included both CD2+ and CD2- phenotypes. This cytotoxicity was not genetically restricted, as cells killed both allogeneic and autologous keratinocytes without priming. Cytotoxicity was blocked by pre-incubation of effector cells with mAb against LFA-1 alpha-(TS1/22) and beta-chains (TS1/18), but not by antibodies directed against CD4, CD8, or leukocyte common Ag (T200) suggesting that LFA-1 is an important interactive molecule in this cytotoxicity. IFN-gamma is reported to upregulate ICAM-1, the ligand for LFA-1. Pre-treatment of target keratinocytes with IFN-gamma was also found to greatly increase the sensitivity of keratinocytes to lysis. This increased sensitivity to lysis was blocked by anti-LFA-1 and anti-ICAM-1, but not by anti-DR (L243), and thus was not the result of increased DR expression. Such treated targets were lysed at low levels (15 to 18%) by an Ag-specific CD8+ cytotoxic clone as well as a T cell line derived from a skin lesion of allergic contact dermatitis. In contrast, control keratinocytes were only sensitive to IL-2-activated PBMC as described above. The above findings may be relevant to a variety of conditions in which epidermal damage is associated with lymphocytic infiltrate. These conditions include graft-vs-host disease, erythema multiforme, and lupus erythematosus. DR+ keratinocytes, which may be a marker for IFN-gamma are also found in the above conditions. It is suggested that epidermal pathology may be mediated by non-specific cytotoxicity induced in the course of an immune response.

Antibodies, Monoclonal↗

Cutaneous adverse reactions associated with calcium channel blockers.

The calcium channel blockers, nifedipine, verapamil, and diltiazem, are widely used for the treatment of cardiovascular disease. In spite of their widespread use, little data about the frequency and spectrum of cutaneous reactions associated with these agents have been published. Based on reports provided to the FDA's Division of Epidemiology and Drug Surveillance, and the American Academy of Dermatology's Adverse Drug Reaction Reporting System, it appears that the frequency of adverse cutaneous events associated with these drugs is low, but that occasionally severe reactions are associated with the use of these drugs. Among the more serious reactions associated with the calcium channel blockers are toxic epidermal necrolysis with diltiazem, Stevens-Johnson syndrome and erythema multiforme, which have been associated with all three drugs in this class, and exfoliative dermatitis, which has also been reported with all three agents. Most serious reactions associated with these agents occur within two weeks of initiating drug therapy. These findings suggest that calcium channel blockers are occasional causes of a wide spectrum of cutaneous reactions and should be considered as possible causative factors in patients who develop adverse cutaneous reactions while using these drugs.

Adult↗

[Atypical dermatomycoses in children as seen in personal observations].

15 cases of cutaneous fungal infection in children with nontypical clinical findings have been presented. The fungal infections simulated other skin diseases particularly atopic dermatitis in 6 cases, diaper dermatitis in 4 cases and in single cases psoriasis, impetigo, purpura, eczema and exudative multiforme erythema. Mycotic examinations have confirmed the fungal character of lesions. The specific treatment resulted in the complete cure of the skin lesions.

Adolescent↗

[Allergic granulomatosis (Churg-Strauss syndrome)].

Allergic granulomatosis is a rare life-threatening systemic disorder of unknown origin, which represents a variant of systemic necrotizing vasculitis affecting medium-sized arteries and venules. Histologically, allergic granulomatosis is characterized by vascular and extravascular necrotizing palisading granulomas with prominent eosinophilia (Churg-Strauss granulomas). The clinical criteria include atopy with severe allergic asthma, pronounced peripheral eosinophilia, and nodular infiltrates of the skin and internal organs (Churg-Strauss granulomas). The internal organs most commonly involved are the lungs, gastrointestinal tract and, less often, the peripheral nerves, heart, and kidneys. Associated symptoms include fever, arthralgias and skin rashes, such as erythema multiforme, necrotizing venolitis, fixed drug eruption, and urticaria. Allergic granulomatosis shares common features with Wegener's granulomatosis and polyarteritis nodosa and may be related to the latter condition; overlap syndromes are a well-known occurrence. Similar to the other manifestations of systemic necrotizing vasculitis, immune complexes have been detected in fresh lesions and are suspected of being the basic pathogenetic findings. The causative antigens are likely to be respiratory antigens. The prognosis of untreated allergic granulomatosis is poor (mortality of approximately 50% within the first year). Systemic corticosteroids and cyclophosphamide are effective; complete remissions following cyclophosphamide treatment have been reported.

Adult↗

Adverse reactions in the skin from anti-hypertensive drugs.

Anti-hypertensive drugs, including diuretics and beta-blocking drugs, belong to a group of therapeutics used by about a fourth of the Danish population. As with cytostatics, antibiotics, and topical remedies, they rather frequently cause adverse drug reactions (ADR) in the skin. No exact statistical information is available concerning the extent of such side effects. The information obtained by Danish National Board of Health's Committee on Adverse Drug Reactions shows that 10-60% of ADR from diuretics, beta-blocking agents, and anti-hypertensive drugs are dermatological. The skin symptoms are not unique for any specific drug. But certain symptoms occur more frequently than others. Thiazides can give vasculitis, a phototoxic/-allergic eruption, erythema multiforme, or eczema. The combination of amiloride (5 mg) and hydrochlorothiazide (50 mg) carries the highest number of recorded ADR; 59% of these are in the skin. Half of the skin ADR are phototoxic eczema. Furosemide may give eczema, purpura, a bullous eruption, or Steven-Johnson's syndrome in rare cases. Methyldopa can induce eczematous eruptions on hands and feet, a lichenoid eruption, a lupus erythematosus-like eruption, or purpura. Hydralazine may give lupus erythematosus-like eruptions, eczema, or urticaria. Non-specific beta-blocking drugs can induce a morbilliform rash and may aggravate psoriasis. Captopril may induce pruritus in up to 15% of the patients and skin eruptions in 2%. The most serious dermatological side effect, exfoliative dermatitis, is very rarely seen following the use of anti-hypertensive drugs or diuretics.

Adrenergic beta-Antagonists↗

Dermatologic emergencies.

Being able to recognize and treat a dermatologic emergency is extremely important to the primary care physician. This ability is very rewarding for the patient and gratifying to the physician. In this article, some of the more commonly encountered emergencies are discussed.

Angioedema↗

[Comparison of complement fixation and Tzanck smear tests for the diagnosis of herpes labialis].

In this study, the serum antibody titer of Herpes simplex virus type 1 (HSV-1) in 82 patients with herpes labialis and 100 controls was determined using the complement fixation test. In own experience, the Tzanck smear test (reported to be an aid in the diagnosis of HSV infection) was of no value. In comparison to patients in an early stage of infection, convalescent patients had an antibody titer that was 4 or more times higher (1/64-1/256). Fifty-eight percent of the control group was negative. In own opinion, the variation in titer between the acute and convalescent stages in Herpes simplex cases would be of particular value in diagnosing cases of urethritis, cystitis encephalitis, meningitis, conjunctivitis, primary and recurrent eczema herpeticum and erythema multiforme when HSV is suspected to play a role in the etiology.

Acute Disease↗

Pregnancy post-Stevens-Johnson syndrome: case report and review of the literature.

A pregnancy complicated by vaginal stenosis six years after diagnosis of Stevens-Johnson syndrome is described. The pathologic changes in the vagina have not previously been reported. The basic pathology of severe mucosal erythema multiforme was present, as well as ectasia of the superficial capillaries and small venules. The effect of the vaginal scars on the mode of delivery is discussed.

Adult↗

Eruptive nevocytic nevi after severe bullous disease.

In two patients, hundreds of nevocytic nevi (melanocytic nevi) appeared in sites of severe bullous dermatoses that were considered to be toxic epidermal necrolysis and erythema multiforme exudativum, respectively. This phenomenon may result from benign melanocytic hyperplasia accompanying keratinocytic hyperplasia during the healing process of some of the denuded areas of the skin.

Child↗