Clinical study of cutaneous drug reactions in 80 patients

Introduction

Drug reactions have become very common in recent times. The incidence of drug reactions is about 2.2% and is higher amongst in-patients and females.[1] Anti-microbial agents are most frequently incriminated (42%) followed by NSAIDS (27%) and drugs regulating CNS function (10%).[1] Fatal reactions to drugs occur even though benign reactions are more common. The incidence increases in proportion to the number of drugs prescribed. The diagnosis of a drug reaction is based on detailed history and the temporal correlation between the onset of the rash and drug intake. Histopathology aids in diagnosis and immunofluorescence locates the nature of immune deposits.

Materials and Methods

The study comprised of 80 cases of drug reaction observed from August 1997 to December 1999. The diagnosis was based on a detailed history and clinical examination. Urticarial pattern of drug eruption was excluded. Histopathological examination was done in 30 cases and direct immunofluorescence (DIF) in 19.

Results

Eighty patients (46 males and 34 Females) were studied. Maximum patienl belonged to age group 21-30 years. Duration lesions ranged from 1 day to 60 days. NSAID were the most implicated drugs in 28 case: followed by antipsychotics in 26, antibiotics in 2~ anti leprotics/antitubercular drugs in 8, steroids i 5, antimitotics in 4 and cardiac drugs in 3. Perio of intake ranged from 1 -30 days with 44 patien having taken for less than 10 days. Maculopapulc was the most common clinical presentation in 4 cases followed by purpura in 7, acneiform in c SJS/TEN and FDE in 5 cases, erythema multiform-in 3, exfoliative dermatitis and AEGP in 2, pustulc and eczematous in 1 each.

Palmoplantar involvement was seen in 2 cases, oral and ocular involvement in 11. A patients with SJS/TEN had oral and oculc involvement. Direct immunofluorescence was dor in 19 cases of maculopapular rash, FDE, SJS or TEN. The most frequent immunoreactant was C in 14 cases, the others being fibrin in 12, IgM 7 and IgG in 6. DIF was negative in pustulc reaction and exfoliative dermatitis. Two cases 1 palpable purpura and SJS had a linear IgG bang IgA was negative.

Histopathological study was done in cases. In maculopapular rash, features range from a normal epidermis to local areas of bas cell degeneration with eosinophilic infiltrat Dermis showed congested vessels, mild moderate perivascular/periappendageal infiltrate of mononuclear cells. Dermal edema, epidermotropism and extravasation of RBCs were also seen. Erythema multiforme showed spongiosis, dermal edema, few necrotic keratinocytes with mild to moderate perivascular infiltrate. Eczematous rash showed non-specific features of elongation of rete-ridges, hyperkeratosis, spongiosis, focal parakeratosis and capillary dilatation with melanin incontinence. Out of 7 cases of palpable purpura, 2 had no features of vasculitis, 5 showed typical features of vasculitis consisting of endothelial swelling, fibrinoid necrosis, extravasation of RBCs and features of vessel damage. TEN had extensive necrotic keratinocytes, subepidermal split, colloid bodies and mild infiltration of mononuclear cells. SJS showed epidermal necrosis with subepidermal split and moderate to strong perivascular inflammatory infiltrate of mononuclear cells and eosinophills. AEGP had heamorrhagic crust with intraepidermal pustule, infiltrate of mononuclear cells and a mild to moderate perivascular infiltrate. Pustular rash revealed acanthosis, hyperkeratosis, foci of spongiosis, exocytosis with predominantly mononuclear infiltrate with neutrophils and eosinophils. Exfoliative dermatitis showed hyperkeratosis, acanthosis, elogation of rete ridges, melanin incontinence with marked perivascular inflammatory infiltrate of mononuclear cells were also seen. Lichenoid drug eruption showed acanthosis, colloid bodies, basal cell degeneration, diffuse infiltration of lymphocytes with occasional eosinophils and features of melanin incontinence. Fixed drug reaction revealed hydropic degeneration of the basal layer, pigment incontinence and exocytosis. The bullous pattern of FDE revealed subepidermal split, dermal edema and perivascular infiltrate of mononuclear cells and eosinophils.

Discussion

Our study had an equal male to female sex ratio as observed in another Indian study.[2] Maximum number of patients were seen in the age group of 21 to 30 years. Paediatric and geriatric age showed a decreased incidence as reported earlier.[2]

The period of drug intake ranged from 1 o 360 days, the mean ranging from 11.33 to 52.12 days. NSAIDS were the most implicated Drugs in 28 cases,followed by antipsychotics in 26, antibiotics in 24, antileprotics / antitubercular in 3, steroids in 5, antimitotics in 4 and cardiac drugs n 3 cases.

Maculopapular rash was the most :ommon clinical presentation as reported earlier.[1],[3] The responsible drugs were antipsychotics (eptoin, aenicillin, sulfonamide, ampicillin, gentamicin, -iorfloxacin and amoxycillin) in 14, NSAIDs indomethacin, ibuprofen and paracetamol) in 13 and ATT drugs in 4 patients. As patients with tuberculosis were on multiple drugs it was not possible to incriminate the particular drug, although it is known that ethambutol and pyrazinamide have a low incidence of reaction. The duration of lesions at the time of presentation ranged from 1-15 days. The period of drug intake ranged from 1-60 days. The trunk, back and extremities were the most commonly involved sites.[4] The histopathological examination aids as a tool to the diagnosis and we have found histopathological features consistent with the type of rash. Immunofluorescence studies help to locate the type of immune deposits. Two cases of palpable purpura had no features of vasculitis as the biopsy may have been done late in the course of the illness. Immunofluorescence finding in cases of maculopapular rash, FDE, SJS and TEN revealed C3 and fibrin to be the commonest immunoreactant.[5],[6] IgA was negative in cases of palpable purpura hence ruling out HSP.