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Year : 1996  |  Volume : 42  |  Issue : 1  |  Page : 15-22  

Adverse cutaneous reactions to drugs: an overview.

VK Sharma, GG Sethuraman 
 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., India

Correspondence Address:
V K Sharma
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

How to cite this article:
Sharma V K, Sethuraman G G. Adverse cutaneous reactions to drugs: an overview. J Postgrad Med 1996;42:15-22

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Sharma V K, Sethuraman G G. Adverse cutaneous reactions to drugs: an overview. J Postgrad Med [serial online] 1996 [cited 2021 Jan 16 ];42:15-22
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Cutaneous adverse drug reactions are not uncommon, affecting 23 percent of hospitalised patients[1]. There is a wide spectrum of cutaneous adverse reactions ranging from transitory exanthematous rash to the potentially fatal Toxic Epidermal Necrolysis (TEN). Drug reactions are not confined to skin but other organs like liver, intestine, central nervous system, joints and bone marrow can also be affected in certain conditions like vasculitis, serum sickness and hypersensitivity reactions like TEN.

  ::   DefinitionTop

An adverse reaction is a reaction which is noxious and unintended and which occurs at dosages normally used in man for prophylaxis, diagnosis or therapy of disease or for the modification of physiological function. This definition is independent of the mechanism of the adverse reaction and includes allergies, idiosyncrasies, pharmacological and toxicological mechanisms and interactions between different drugs[2]. In the case of clinical trials injuries by overdosing, abuse/dependence and interactions with other medicinal products should be considered adverse drug reactions[3].

  ::   Incidence of adverse drug reactionsTop

Various adverse cutaneous drug reactions have been found in 23 percent of hospitalised patients. Many of the commonly used drugs have reaction rates above 1 percent. Most of the times adverse cutaneous reactions are not severe enough and only a few are fatal[4].

Complications of drug therapy are the most common type of adverse event in hospitalised patients, accounting for 19 percent of such events[5]. The reported percentage of cutaneous reactions that physicians diagnose as "Potentially Serious" varies greatly and is estimated to be above 2 percent[6],[7].

Classification and mechanism of adverse drug reactions:

Adverse drug reactions [8],[9],[10],[11],[12],[13],[14],[15] may arise as a result of Immunological or nonimmunological mechanisms, the latter being more common which may be predictable (type A) or unpredictable

(type B).

* Type A (predictable) reactions: These are due to known pharmacological actions of the drugs and usually dose related which occur in otherwise normal individuals. Predictable drug reactions include toxicity or overdose, side effects, drug interactions and secondary effects.

* Type B (unpredictable) reactions: Unpredictable reactions are dose independent, not related to the pharmacological actions of the drug and may have a genetic basis. These reactions are divided into three categories: intolerance, idiosyncratic reaction and hypersensitivity reaction. Intolerance refers to an expected drug reaction occurring at a lower dose whilst idiosyncratic and hypersensitivity reactions are qualitatively abnormal unexpected responses.

* Type C reactions include those associated with prolonged therapy e.g. analgesic nephropathy.

* Type D reactions consist of delayed reactions e.g. carcinogenesis and teratogenesis.

Classification of Adverse Drug Reactions

1. Non Immunological

A. Predictable B. Unpredictable

Over dosage Intolerance

Side effect Idiosyncrasy


Delayed toxicity

Facultative effect

Drug interaction


NonImmunological activation

of effect or pathways

Exacerbation of disease

Drug induced chromosomal damage

2. Immunological (Unpredictable)

IgE dependent drug reaction

Immune complex reaction

Cytotoxic reaction

Cell mediated reaction

3. Miscellaneous

Jarisch Herxheirner reaction

Infectious mononucleosis ampicillin reaction

Factors influencing adverse drug reactions

1. Age: Drug reactions are considered to be rare in infants and children[16]. Though allergic reactions are considered to be less common in aged people due to dampening of Immunological responsiveness[8], adverse drug reactions occur frequently with increasing age, especially in those above 65 years. Factors which may predispose elderly to adverse drug reactions, includes polypharmacyage associated changes in pharmacokinetics and pharmacodynamics, altered homeostasis, multiple pathology and use of drugs with a narrow therapeutic margin[17].

2. Sex: Cutaneous reactions are more frequent among women[18].

3. Underlying diseases:

* Presence of infectious mononucleosis increases the risk of hypersensitivity skin rash to ampicillin or its analogues[19],[20],[21],[22],[23],[24].

* Human Immunodeficiency Virus (HIV) increases the propensity for sulfonamide rash[25].

* Preexisting diseases[26] (impaired hepatic and renal function) increase the risk of development of drug rashes.

4. Genetic: Genetic or constitutional factors are important in drug reactions.

* Toxic epidermal necrolysis has been shown to be associated with HLAB 12; TEN due to sulfonamides with HLAA29, B12 and DR7; and oxicamrelated TEN with HILAA2 and A12[27].

* Erythema multiforme has been associated with 3. HLA B 62 (B15), HLA B35 and HLA A33, HLA DR53, HLA DQB1* 0301 2832. Recurrent erythema multiforme has been shown to be strongly associated with HLA DQB[33].

* A recent report from Italy also suggested a strong association of FDE with HLAB22 and CW1 antigen[34].

5. Multiple drugs: Use of multiple drugs is associated with higher incidence of drug reactions as observed with increased frequency in hospitalised patients[5].

6. Drugs: Certain drugs are associated with higher incidence of drug reaction eg. amoxycillin in 5.1 %, ampicillin in 3.3% and cotrimoxazole in 3.2%[1].

Clinical manifestations of cutaneous adverse drug reactions:

1. Exanthematous (maculopapular) rash: It is the most frequent of all cutaneous reactions to drugs and may occur with almost any drug at any time upto three weeks (but usually two) after administration. The clinical features are variable which may be morbilliform or scariatiniform or rubelliform. They may consist of profuse eruptions of small papules or purpuric lesions, which are usually associated with severe pruritus. The distribution is generally bilaterally symmetrical involving trunk and extremities. Maculopapular eruptions usually fade with desquamation, sometimes with post inflammatory hyperpigmentation[31].

Ampicillin, amoxycillin and sulphonamides are amongst the most frequent causes[36], other common drugs indlude phenytoin carbamazepine, NSAIDS and ciprofloxacin[35]. Less common drugs: cephalosporins, barbiturates, thiazides. INK phenothiazines, naproxen and quinidine[35].

2. Fixed Drug eruption (FDE): FDE are characterized by a single or a few sharply demarcated erythematous lesions, which resolve promptly but the local hyperpigmentation remains. Face, genitalia and the extremities are commonly affected. It characteristically recurs in the same site or sites each time the drug is administered: with each exposure however the number of involved sites may increase. The drugs that frequently have been associated with FDE are sulfonamides especially cotrimoxazole, NSAIDS, phenolphthalein, tetracyclines[37],[38],[39],[40],[41],[42],[43] and ciprofloxacin[44].

3. Urticaria/angioedemalanaphylaxis: Immediate hypersensitivity reactions can produce a range of cutaneous findings from simple urticaria to angioedema or fatal anaphylaxis[2]. Most urticarial and angioedema reactions caused by antibiotics are I9E mediated with the exception of polymyxin B and vancomycin, which directly release histamine from mast cells and basophils. Penicillin is the most common drug but other antibiotics including sulphonamides, cephalosporins and tetracyclines, as well as diuretics, tranquilizers, analgesics, muscle relaxants and anti hypertensives may be responsible. Morphine, codeine, doxorubicin, certain muscle relaxants like dtubocurarine, and ionic radiocontrast dyes all cause mast cell degranulation. Urticaria and angioedema due to aspirin and other cyclooxygenase inhibitors is probably due to an imbalance between prostaglandin and leukotriene production. Urticaria manifests as severely pruritic circumscribed raised, oedematous and erythematous wheals widely scattered on the body. It may accompany systemic anaphylaxis or serum sickness. Urticaria lesions rarely persist for more than 24 hours[45],[46],[47]. Angioedema involving edema of the deep dermis or subcutaneous and submucosal areas is less commonly seen than urticaria as an adverse drug reaction with the exception of ACE inhibitors in which angioedema is more frequent during initial weeks of therapy[48].

4. Vasculitis: It is characterized by inflammation and necrosis of small vessel walls, having multiple etiologies and drugs cause about 10 percent of cases of acute cutaneous vasculitis. It usually develops 721 days after a new drug is begun and is clinically characterized by palpable purpura predominantly of the lower extremities. The other less common manifestations include erythematous macules, haemorrhagic vesicles, papules, wheals, blisters, ecchymoses and large palpable nodules. It may involve other organs including kidneys, liver, joints, CNS and pericardium. Histologically there is swelling of endothelial cells, fibrinoid necrosis, neutrophilic infiltrate within and around the blood vessel and nuclear dust[49],[50],[51],[52]. The direct immunoflourescence is more often positive with deposits of IgM and C3 and fibrin in and around the capillaries[4].

Drugs most often implicated in causing vasculitis are allopurinol, penicillin. aminopenicillins, sulphonamides, thiazides, pyrazolones, hydantoin, propylthiouracil, streptomycin, phenothiazine. aminosalicylic acids, vitamins, tamoxifen and oral contraceptive pills[52].

5. Serum sickness: It is a type 3 hypersensitivity reaction mediated by the depositions of immune complexes in small vessels, activation of complement and recruitment of granulocytes. Serum sickness in its usual form is characterised by fever, urticaria (lasting for more than 24 hours), angioedema, arthralgia and/or arthritis and lymphadenopathy. About half the cases of serum sickness, have visceral involvement. In serum sickness C3 and C4 complement levels are markedly decreased. It may be produced by drugs like penicillin, streptomycin, sulphonamides, thiouracil, diphenyil hydantoin and aminosalicylic acid[18],[53],[54],[55].

6. Hypersensitivity syndrome: It is a severe idiosyncratic reaction characterized by skin rash and fever, often associated with hepatitis, arthralgia, lymphadenopathy or haematological abnormalities. It usually develops two to six weeks after the drug is first administered. The drugs associated with this syndrome include antiepileptic agents, dapsone, allopurinol, gold and sorbinil. Recovery is usually total but rash and hepatitis may persist for weeks. Treatment with steroids has been widely advocated but controlled studies are lacking[4].

7. Erythema Multiforme/Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis: Originally it was widely accepted that EM minor, EM major, Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were all part of a single “EM spectrum”[56]. But recently a consensus clinical classification was proposed, based on the pattern of skin lesions and the extent of epidermal detachment". Accordingly. EM (minor or major) could be one disorder, which is mainly caused by herpes virus infection and sometimes by other infectious diseases, but rarely, if ever by drugs. On the other hand. SJS, TEN and overlap (SJS/TEN) are probably severe variants of a single disorder mainly if not exclusively caused by drugs[57],[58].

i. Diagnostic criteria for EM:

* An acute self-limiting illness

* Duration of episode less than four weeks

* Symmetrically and acrally distributed, typical or raised atypical target lesions.

* Absent or limited mucosal involvement.

* Recurrent episodes.

ii. Stevens Johnson Syndrome: It is a serious mucocutaneous illness with systemic symptoms and signs with significant mortality[59],[69], characterized by the presence of flat atypical target lesions or purpuric macules with blisters that are distributed mainly on the trunk or widespread and the epidermal detachment being less than ten percent of body surface area (BSA). Two or more mucosal sites can be involved [57],[58].

iii. Toxic Epidermal Necrolysis: It is a life threatening illness characterized by high fever and confluent erythema followed by necrolysis. The epidermal detachment is more than 30 per cent of BSA. Patients with this condition may also have flat atypical target lesions (TEN with spots). Rprelly extensive epidermal necrosis occurs without any discrete target lesion (TEN without Spots)[57].

iv. In the overlap category (SJS/TEN) the area of epidermal detachment, which is often much less than the area of erythema, is between 10 and 30% of the BSA[57].

Drug induced SJS and TEN typically begin one to three weeks after the initiation of therapy

Drugs associated with SJS and TEN[10]

Drugs commonly associated Other drugs

Thioacetazone Allopurinol

Isoniaid Barbiturates

Diphenylhydantoin Chlorpromazine

Carbamazepine Erythromycin

Phenylbutazone Rifampicin

Cotrimoxazole NSAIDs

Ampicillin Salicylates

Oxytetracycline Oxyphenbutazone





8. Exfoliative Dermatitis: It may follow exanthematous eruptions or may develop as erythema and exudation in the flexures, rapidly generalizing. It is a serious condition and can be life threatening in elderly patients. It takes 4 of 6 weeks to subside even after withdrawal of drugs. The most frequently encountered drugs include sulfonamides, antimalarials, penicillin, INK thioacetazone and a variety of homeopathic preparations. Recently incriminated drugs are Captopril, Cefoxitin and Cimetidine[71],[72],[73].

9. Pseudolymphomatous eruptions: The pseudolymphoma syndrome is associated with a number of anticonvulsant drugs and is characterized by fever, generalized rash, lymphadenopathy, hepatosplenomegaly, abnormal liver function tests, arthralgia, eosinophilia and dyscrasias. This condition usually responds to drug withdrawal[71],[72],[73],[74],[75],[76],[77]. Common drugs: Phenytoin, Mepheloin, Trimethadione and Phenobarbitone

10. Miscellaneous:

a) Acneiform eruptions may be caused by steroids, ACTH, INH, Iodides, Bromides, dantrolene, danazol, quinidine, lithium and azathioprine. Lesions usually are monomorphic and comedones are absent [80],[81],[82],[83],[84],[85].

b) Lichenoid drug reactions (LDE): skin eruptions caused by certain drugs and compounds can be identical or similar to lichen planus. An LDE may have eczematous papules and generalized eczematous skin reactions with marked desquamation. The lesions are symmetrical, larger, and psoriasiform and often have a photo distribution. Mucosae are less commonly involved[86],[87],[88],[98].

Inducers of LDE, gold salts, antimalarials, diuretics, calcium channel blockers, heavy metals etc.

c) Drug induced pigmentation results from increased melanin synthesis, increased lipofuscin synthesis, cutaneous deposition of drug related material or most commonly as a result of post inflammatory hyperpigmentation[99],[100],[101].

Drugs causing pigmentation: oral contraceptives, minocycline, antimalarials (chloroquine and mepacrine), chlorpromazine, clofazimine, gold and lead.

d) Other reactions include photosensitivity, pruritus, hypertrichosis, photoonycholysis, bullous eruptions, alopecia, erythema nodosum, allergic eczematous dermatitis, systemic eczematous "contact type" dermatitis and pityriasis rosea like eruptions.

Drug reactions in children and adolescents:

The frequency of drug rash is low in the younger age group, probably because of less cumulative drug exposure, rapid dissipation of IgE compared to adults and poorly developed immunopathologic mechanisms like impaired T cell reactivation, diminished production of lymphokines, decreased chemotactic activity of macrophages and less functional competence of NK cells. The frequency of adverse cutaneous reactions in hospitalised children is 2 to 3 %, The common drug reaction patterns include maculopapular rash, fixed drug eruption and erythema multiforme and the commonly implicated drugs are antibiotics, antiepileptics drugs, antiemetics, bronchodilators, vaccines, antipyretic, analgesics and drugs used for preanaesthetic medication[16],[102],[103],[104],[105],[106],[107].

  ::   Evaluation of adverse drug reactions; a stepwise approachTop

First Step: History and Physical Examination:

* Temporal correlation with the drug

* Incubation period (interval between the introduction of the drug and the onset of reaction)

* Clinical pattern of the eruption

* Any improvement on drug withdrawal

* Any reaction on re-administration of the drug

Second Step: In vivo Testing

i) Rechallenge (Test Dosing): A positive rechallenge is generally accepted as strong evidence for causality. Reexposure should not be performed after a serious reaction. If a reaction fags to recur on rechallenge. it may be due to the fact that the previous reaction was a result of drug interaction[108].

ii) Patch Testing: It is a well-known method of rechallenging the skin in conditions when cell mediated immunity is suspected vizmaculopapular eruptions[109], FDE[110], exfoliative dermatitis[111] and lichenoid dermatitis[112].

iii) Dechallenge: Most adverse reactions to drugs should remit with dechallenge i.e. withdrawal of the drugs[108].

Third Step: In Vitro Testing

Immunoassays such as radioallergosorbent lest (RAST) and Enzyme linked Immunosorbent Assays (ELISA) are in varying stages of development for the detection of IgE to aminoglycosides, penicillin, sulfonamides, ACTH etc. Other tests include Lymphocyte Transformation Test (LTT), Macrophage Migration Inhibition Factor Test (MIF), Lymphocyte Toxicity Assay (LTA), Basophil Degranulation Test, Histamine Release Test, Haemagglutination Assays 108 and flowcytometry. But unfortunately most in vitro tests 3 are unreliable for routine clinical use and are suitable only for immunologic research.

  ::   ManagementTop

Basic principles:

* Stop the offending drug or all drugs

* Assess the type of rash and percentage involvement

* Symptomatic treatment (antihistamines) for minor reactions

* Steroids for major reactions like SJS, TEN and exfoliative dermatitis.

Short courses of steroids have been advocated in severe maculopapular reactions, erythema multiforme and Stevens Johnson or overlap syndromes especially early in the disease (within 48 hours of the onset of the disease)

Though the role of steroids in TEN is controversial[113], their restricted use in preexfoliative cases, slowly evolving cases of those in which the necrolysis has started on newly regenerated skin, has been found beneficial. The rationale for the use of steroids is based on the concept that TEN is due to a delayed hypersensitivity reaction or antibody dependent cytotoxicity and also their inhibitory action against the secretion of Tumour necrosis factor.

* Antiviral therapy in case of HSV induced EM[114]

* Monitoring of vitals

* Fluid and electrolyte maintenance Desensitization: when no alternative drug is available, it is possible to induce a state of antigen specific mast cell unresponsiveness in patients with Type 1 IgE mediated reactions especially to penicillin.

  ::   ConclusionTop

The severity of cutaneous adverse drug reactions is variable with TEN and SJS having a fatality rate of 3040 percent. Severe drug reactions like SJS and TEN need to be identified early for the prompt treatment. High index of suspicion is required for early diagnosis and appropriate management.


1 Bigby M, Jick SJ, Kien H, Amdt K. Druginduced cutaneous reactions a report from the Boston Collaborative Drug Surveillance Program on 15. 438 consecutive in patients 1975 to 1982. JAMA 1986; 256:33583363
2World Health Organization international Drug Monitoring 1972. The role of national centres. Technical Report Series 498 Geneva.
3EEC note for guidance: Good clinical practice for trials on medicinal products in the European community. In: Lloyd J, Raven A, editors. Handbook of Clinical Research. London: Churchill Livingstone, 1994, pp 436.
4Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N EngI J Med 1994; 331:12721285.
5Leape LL, Brennan TA, Laird N. The nature of adverse events in hospitalised patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991; 324:377384.
6Alanko K, Stubb S, Kauppinen K. Cutaneous drug reactions, Clinical types and causative agents in a fiveyear survey of in patients (19811985). Acta Derm Venereol (Stockh) 1989; 69:223226.
7Ives TJ, Bentz EJ, Gwyther RE. Dermatologic adverse drug reactions in a family medicine setting. Arch Fam Med 1992; 1:241245.
8Van Arsdel PP. Allergy and adverse drug reactions. J Am Acad Dormatol 1982; 6:833845.
9Parker CW. Allergic reactions in man. Pharmacol Rev 1983; 34:85194.
10Wintroub BU, Stern R. Cutaneous drug reactions: pathogenesis and clinical classification. J Am Acad Dermatol 1985; 13:833-845.
11De Swarte RD. Drug allergy: An overview. Clin Rev Allergy 1986; 4:143169.
12Stern RS, Wintroub BU, Arndt KA. Drug reactions. J Am Acad Deanatol 1986; 15:12821288.
13Blaiss MS, de Shazo RD. Drug allergy. Pediatr Clin North Am 1988; 35:11311147.
14Park BK, Coleman JW. The immunological basis of adverse drug reactions. A report on a Symposium held in Liverpool on 6th April 1988. Br J Clin Pharmacol 1988; 26:491495.
15Kalish RS. Drug eruptions: a review of clinical and Immunological features. Adv Dermatol 1991; 6:221237.
16Sharma VK, Dhar S. Clinical pattern of cutaneous drug eruption among children and adolescents in North India. Ped Dermatol 1995; 12:178183.
17Nolan L, O'Malley K. Adverse drug reaction in the elderly. Br J Hosp Med 1989; 41:446457.
18Blacker K, Stern R, Wintroub BU. Cutaneous reactions to drugs. In: Fitzpatrick T Eisen A, Wolft K, editors. Dermatology in general medicine. New York: McGrawHill; 1993, pp 17831794.
19Patel BM. Skin rash with infectious mononucleosis and ampicillin. Paediatrics 1967; 40:910.
20Pullen H. Hypersensitivity reactions to antibacterial drugs in infectious mononucleosis. Lancet 1967; 2:1176.
21Levene G, Baker H. Drug reactions: ampicillin and infectious mononucleosis. Br J Dermatol 1968; 80:417.
22McKenzie H. IgM and IgG antibody levels to ampicillin in patients with infectious mononucleosis. Clin Exp Immunol 1976; 26:214
23Mulroy R. Amoxycillin rash in infachous mononucleosis. Br Mod J 1973; 1:554.
24Morris J. Infectious mononucleosis rash after Talampicillin. Lancet 1976; 1:423.
25Gordin FN, Simon GL, Wofsy CD. Adverse reactions to trimethoprimsulfamethoxazole in patients with the acquired immunodeficiency syndrome Ann Intern Med 1984; 100:495-499.
26Bookar HE. Idiosyncratic reactions to antiepileptic drugs: Epilepsia 1975; 16:171181.
27Roujeau X, Huynh TN, Bracq C, Guilluame JC, Revuz J, Touraine R. Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 1987; 123:11711173.
28Duvic M, Reisner EG, Dawson DV, Ciftan E. HLA1315 association with erythema multiforme. J Am Acad Dermatol 1983; 8:493496.
29Middleton D, Hutchinson TH, Lynd J. HLA antigen frequency in erythema multiforme and in recurrent herpes simplex. Tissue Antigens 1983; 21:264267.
30Kampgen E, Burg G, Wank R. Association of herpes simplex virus induced erythema multiforme with the human leukocyte antigen DQw3. Arch Dermatol 1988; 124:13721375.
31Lepage V, Douay C, Mallet C. Erythema multiforme is associated to HLAAw33 and Drw53. Tissue Antigens 1988; 32:170175.
32Khalil I, Lepage V, Douay C. HLAD (DQB*0301 allele is involved in the susceptibility to erythema multiforme. J Invest Dermatol 1991; 97:697700.
33Schofield JK, Tatnall FM, Brown J. Recurrent erythema multiforme: tissue typing in a large series of patients. Br J Dermatol 1994; 131:532535.
34Pellicano R, Ciavarelia G, Lomuto M, Di Giorgio G. Genetic susceptibility to fixed drug eruption. Evidence of link with HLA B22. J Am Acad Dermatol 1994; 30:5254.
35Types of clinical reactions. In: Breathnach SM, Hintner H, editors. Adverse drug reaction and the skin. Oxford: Blackwell Scientific Publications, 1992, pp 4144.
36Porter J, Jick H. Amoxicillin and ampicillin rashes equally likely. Lancet 1980; i:1037.
37Savin J. Current causes of fixed drug eruptions. Br J Dermatol 1970; 83:546549.
38Sehgal UN, Rege VL, Kharangate UN. Fixed drug eruptions caused by medications: a report from India. Int J Dermatol 1978; 17:7881.
39Pashcha JS. Drugs causing fixed eruptions. Br J Dermatol 1979; 100:183185
40Shukla SR. Drugs causing fixed eruptions. Dermatological 1981; 163:160163.
41Sehgal VN. Gangwani OP. Fixed drug eruption: Current concepts. Int J Dermatol 1987; 26: 6774.
42Korkij W, Soltani K. Fixed eruption. A brief review. Arch Dermatol 1984; 120: 520524.
43Kauppinen K, Stubb S. Fixed eruptions: causative drugs and chadlenge tests. Br J Dermatol 1985; 112:575578.
44Dhar S, Sharma VK. Fixed drug eruption due to ciprotioxacin. Br J Dermatol 1996; 134:156158.
45Black AK, Greaves MW, Champion RH. The urticarias 1990. Br J Dermatol 1991; 124:100.
46Healy DR, Sahai JV, Fuller SH. Vancomycininduced histamine release and “Yed man syndrome”. Comparison of 1 and 2 hour infusions, Antimicrob Agents Chemother 1990; 34:550.
47Narth FC, Kettlekamp N, Hirschman CA. Comparison of cutaneous and in vitro histamine release by muscle relaxants. Anesthesiology 1987; 66:543.
48Slater EE, Werrill DD, Guess HA. Clinical profile of angioedema associated with angiotensin converting enzyme inhibition. JAMA 1988; 260:967.
49Fauci AS, Haynes B, Katz P. The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic consider actions Ann Intern Med 1978; 89:600676.
50Ekenstarn EAF, Callen JP. Cutaneous leukocytoclastic vasculitis clinical and laboratory features of 82 patients seen in private practice. Arch Dermatol 1984; 120:484489.
51Sanchez NP, Van Hale HM, Su WP. Clinical and histopathologic spectrum of necrotizing vasculitis: report of findings in 101 cases. Arch Dermatol 1985; 121:220224.
52Lotti T, Comacchi C, Ghersetich I. Cutaneous necrotizing vasculitis. Int J Dermatol 1996; 35:457474.
53Lawley TJ, Bielory L, Gascon P. A prospective clinical and immunologic analysis of patients with serum sickness. N Engl J Med 1984; 311:14071413.
54Bielory L, Yancey KB, Young NS. Cutaneous manifestations of serum sickness in patients receiving antithymocyte globulin. J Am Acad Dermatol 1985; 13:411417.
55Erffmeyer JE. Serum sickness. Ann Allergy 1986; 56:105-109.
56Huff JC, Weston WL, Tonnesen MG. Erythema multiforme: a critical review of characteristics, diagnostic criteria and causes, J Am Acad Dermatol 1983; 8:763775.
57BastupGarin S, Rzany B, Stern RS. Clinical classification of cases of toxic epidermal necrolysis, StevensJohnson Syndrome and erythema multiforme. Arch Dermatol 1993; 129:9296.
58Assier H, BastujiGarin S, Revuz J. Erythema multiforme with mucous membrane involvement and StevensJohnson syndrome are clinically different disorders with distinct causes. Arch Dermatol 1995; 131:539543.
59Ting HQ, Adam BA. StevensJohnson syndrome. A review of 34 cases. Int J Dermatol 1985; 30:58791.
60RuizMalclonado R. Acute disseminated epidermal necrosis types 1, 2 and 3: study of sixty cases. J Am Acad Dermatol 1985; 13:623 635.
61Lehtinen H, Malmstrom M, Stubb S. Erythema exudativum multiforme and Stevens Johnson syndrome. Proc Finn Dent Soc 1986; 82:119126.
62Molin I. Oral acyclovir prevents herpes simplex virus associated erythema multiforme. Br J Dermatol 1987; 116:109111.
63Schopf E. Skin reactions to cotrimoxazole. Infection 1987; 15:52545258.
64Bianchine JR, Macaraeg M Jr., Lasagna L. Drugs as etiologic factors in StevensJohnson syndrome. Am J Med 1968; 44:390405.
65Crosby SS, Murray KM, Marvin JA. Management to Stevens Johnson syndrome. Clin Pharmacol 1986; 5:682-689.
66Roujeau C. Clinical aspects of skin reactions to NSAIDS. Scand J Rheumatol 1987; 65:131134.
67Halebian R, Cordet V, Herndon D. A burn center experience with toxic epidermal necrolysis J Burn Care Rehab 1983; 4:176183.
68Kim PS, Goldfarb M, Gaisford JC. Stevens Johnson syndrome and toxic epidermal necrolysis: A pathophysiologic review with recommendations for a treatment protocol. J Burn Care Rehab 1983; 4:91100.
69Demling RH, Ellerbe S, Lowe NJ. Burn unit management of toxic epidermal necrolysis. Arch Surg 1978; 113:758759.
70Bilimoria FE. Shah PP. Drug reactions. In: Valia RG, Valia AR, Siddappa K, editors. IADVI Test Book and Atlas of Dermatology. Bombay: Bhalan Publishing House 1994; 11361161
71Nicolis GD, Helwig EB. Exfoliative dermatitis. A clinicopathologic study of 135 cases, Arch Dermatol 1973; 108:788797.
72Hasan T, Jansen DT. Erythroderma: A followup of fifty cases. J Am Acad Dermatol 1983; 8:836840.
73Sehgal VN, Srivastava G. Exfoliative dermatitis. A prospective study of 80 patients. Dermatological 1986; 173:278284
74Saltystein SL, Aukerman LI. Lymphadenopathy induced by anticonvulsant drug &nd mimicking clinically and pathologically malignant lymphoma. Cancer 1959; 12:164182.
75Clinicopathologic conference. Lymphoma or drug reaction occurring during hydantoin therapy for epilepsy. Am J Med 1962; 32:286292.
76Sparberg M. Diagnostically confusing complications of diphenylhydantoin therapy. A review. Ann Int Med 1963; 59:914-930.
77Schrieber MM, McGreger JG. Pseudolymphoma syndrome. A sensitivity to anticonvulsant drugs. Arch Dermatol 1968; 97:297300.
78Charlerworth EN. Phenytoin induced pseudolymphoma syndrome. Arch Dermatol 1977; 113:477480.
79Kardaun SH, Scheffer E, Vermeer BJ. Drug induced pseudolymphomatous skin reaction. Br J Dermatol 1988; 118: 545552.
80Burkhart CG. Quindine induced acne. Arch Dermatol 1981; 117:603604.
81Cohen LK, George W, Smith R. Isoniazid induced acne and pellagra. Occurrence in slow inactivators of isoniazid. Arch Dermatol 1974; 109:377381.
82Greenberg RD. Acne vulgaris associated with antigonadotrophic (danazol) therapy. Cutis 1979; 24:431432.
83Hitch JM. Acneiform eruptions induced by drugs and chemical. JAMA 1967; 200:879880.
84Hurwitz RM. Steroid acne. J Am Acad Dermatol 1989; 21:11791181.
85Pembroke AC, Saxena SR, Kataria M. Acne induced by dantrolene. Br J Dermatol 1981; 104:465468.
86Savage J. Lichenoid dermatitis due to chloroquine. Br J Dermatol 1958; 70:181.
87Anderson TE. Lichen planus following quinidine therapy. Br J Dermatol 1967; 79:500.
88Bonnetblane JM, Bernard R, Catanzano G. Quinidine induced lichenoid photodermatitis. Ann Dermatol Venereol 1987; 114:957 961.
89Berger TG, Sesody ST. Quinidine induced lichenoid photodermatitis Cutis 1982; 29:595597, 600.
90Haim S, FriedmanBimbaum R, Gilhar A. Lichenoid skin eruption due to quinidine. Harefauh 1981; 101:310311.
91Seehafer JR, Rogers RS III, Fleming CR. Lichen planus like lesions caused by penicillamine in primary biliary cirrhosis Arch Dermatol 1981; 117:140142.
92Van Heeke E, Kint A, Temmerman L. A lichenoid eruption induced by penicillamine. Arch Dermatol 1981; 117:676677.
93Halevy S, Grunwald MH, Feuerman EJ. Lichenoid eruption due to hydrochforothiazide. Diagnostic aid of macrophage migration inhibition factor (MIF) test Ann Allergy 1986; 56:402405.
94Downham TF. Spironolactone induced lichen planus (Letter) JAMA 1978; 240:1138
95Hodl S. Side effects of beta-receptor blockers on the skin: review and personal observations Hautarzt 1985; 36:549557.
96Hawk JLM. Lichenoid drug eruptions induced by propranolol. Clin Exp Dermatol 1980; 5:9396.
97Rotstein E, Rotstein H. Drug eruptions with Lichenoid histology produced by captopril. Australas J Dermatol 1989; 30:9-14.
98Halevv S, Shai A. Lichenoid drug eruptions. Clinical Review. J Am Acad Dermatol 1993; 29:249253.
99Levantine, Almeyda J. Drug reactions: XXII. Drug induced changes in pigmentation. Br J Dermatol 1973; 89:105112.
100Granstein RD, Sober AJ. Drug and heavy metal induced hyperpigmentation. J Am Acad Dermatol 1981; 5:118.
101Fefguson J, FrainBell W. Pigmentary disorders and systemic drug therapy. Clin Dermatol 1989; 7:4454.
102McKenzie MW, Marchall GL, Netzioff ML. Cluff LE Adverse drug reactions leading to hospitalization in children. J Pediatr 1976; 89:487490.
103Mitchell AA, Goldman P, Shapiro S, Stone D. Drug utilization and reported adverse reactions in hospitalized children. Am J Epidemiol 1979; 110:196204.
104Choonara MS, Harris F. Adverse drug reactions in medical inpatients. Arch Dis Child 1984; 59:578580.
105Ramer MS, Hutchinson TA, Flegel KM, Naimark L, Contariji R, Leduc DG. Adverse drug reactions in general paediatric outpatients. J Pediatr 1985; 106:305.
106Dharnidharka VR, Kandoth P, Anand RK. Adverse drug reactions in paediatrics with a study of inhospital intensive surveillance. Indian Pediatr 1993; 30:745751.
107Karande SC, Kshirsagar NA. Adverse drug reactions in children in developing countries. Natl Med J India 1996; 9:218-221.
108Sacerdoti G, Vozza A, Ruocco V. Identifying skin reactions to drugs. Int J Dermatol 1993; 32:469479.
109Burynzeel D, Van Ketel W. Skin test in the diagnosis of maculopapular drug eruptions in allergic contact dermatitis. Semin Dermatol 1987; 6:119124.
110Alanko K, Stubb S, Reitano S. Topical provocation of fixed drug eruption. Br J Dermatol 1987; 116:561567.
111Camarasa JG. Patch test diagnosis of exfoliative dermatitis due to carbamazepine. Contact Dermatitis 1985; 12:49.
112Lundstrom IMC. Allergy and corrosion of dental materials in patients with oral lichen planus. Int J Oral Surg 1984; 13:1624.
113Arsons JM. Toxic epidermal necrolysis. Int J Dermatol 1992; 31:749776.
114Backman KS, Patterson R. An erythematous rash preceding ulcerative oral lesions in a 41yearold woman. Ann Allergy, Asthma & Immunol 1996; 76:500506.

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