INTRODUCTION :
A drug may be defined as a chemical substance, or combination of
substances, administered for the investigation, prevention or treatment of
diseases or symptoms, real or imagined. An adverse drug reaction (ADR) may
be defined as an undesirable clinical manifestation resulting from administration
of a particular drug; this includes reactions due to overdose, predictable side
effects and unanticipated adverse manifestations. ADR can also be defined as
‘an appreciably harmful or unpleasant reaction, resulting from an intervention
related to the use of a medicinal product, which predicts hazard from future
administration and warrants prevention or specific treatment, or alteration of the
dosage regimen, or withdrawal of the product’. ADRs are underreported and are
an underestimated cause of morbidity and mortality; it has been estimated that
ADRs represent the fourth to the sixth leading cause of death.
Adverse Cutaneous Drug Reactions (ACDRs) are probably the most
frequent manifestations of all drug sensitivity reactions although their incidence
is difficult to determine. Very few published studies have assessed the
epidemiological and clinical features of drug reactions in India and still fewer in
South India. Hence this study was undertaken to assess the pattern and clinical
features of ACDRs and common drugs causing them in South Tamilnadu.
AIM OF THE STUDY :
1. To study the clinicoepidemiological pattern of various adverse cutaneous drug
reactions in patients attending SKIN OPD, Government Rajaji Hospital.
2. To study the common drugs causing adverse cutaneous drug reactions.
MATERIALS AND METHODS :
This study was a prospective, observational study conducted at the skin
OPD, Government Rajaji Hospital, Madurai Medical College, Madurai during
the period from October 2009-September 2011[24 months].
Inclusion criteria:
All consecutive consenting patients diagnosed clinically as a case of
adverse cutaneous drug reaction of all age groups, of all genders, during the
study period were included in the study.
Exclusion criteria:
Non consenting patients, and patients with morphological pattern of
adverse cutaneous drug reaction, but were unable to provide an exact history of
drug intake.
Patients satisfying the criteria were included in the study and demographic
details were recorded. A detailed clinical history including duration, site of
onset, symptoms, drug history, family history were elicited. A complete general
examination, systemic examination and dermatological examination were made.
Digital photographs were taken. The morphology and distribution of skin lesions,
concomitant affection of mucosa, hair, nails, palms, soles, genital involvement
was meticulously recorded and presence of any other associated diseases were
noted.
SUMMARY :
1) Incidence:
Out of all patients attending SKIN OPD during the study period of 24
months 163 patients were diagnosed with ACDR, which constituted to 0.15 %.
2. Occurrence of various clinical types of ACDRs :
Out of the total 163 patients FDE was the most common ACDR seen in 84
cases, Urticaria and Maculopapular rash in 15 cases each, Erythroderma in 11
cases, Urticaria with angioedema in 10 cases, DRESS & SJS in 7 cases, TEN in
6 patients, EMF in 5 patients, Acneiform eruptions in 2 cases and a single case
of phototoxic reaction.
3. Age distribution in various ACDRs:
The maximum no. of cases that is 39.87% of patients were falling between
31-50 years of age group. The youngest patient was 3 months old & oldest
patient was 75 years.
4. Gender distribution in ACDRs:
An almost equal incidence of occurrence in both males & females was
noted, with a slight male predominance.82 cases were males & 81 cases were
females.
5. Site of involvement in various types of ACDRs :
84 patients had only cutaneous involvement.Both cutaneous and mucosal
involvement was seen in 79 out of 163 patients. Out of these 49 had oral
mucosal involvement only, 5 had genital mucosal involvement only, 24 had
both oral and genital mucosal involvement.
6. Recurrent episodes in various types of ACDRs:
Recurrent episodes were seen in 76 patients out of 163. DRESS, TEN,
Erythroderma, Acneiform eruption and phototoxic reaction patients never had
any previous episodes of recurrences.
7. Various drug classes involved in ACDRs:
The commonest drug class involved was antimicrobials with 11 drugs,
followed by NSAIDs with 7 drugs, next common was anticonvulsants with 3
drugs and least common was seen with antidepressants and cancer chemotherapy
with a single drug.
8. Drugs commonly involved in ACDRs:
Cotrimoxazole was the commonest drug causing ACDR which was found
in 37 cases followed by Phenytoin and Doxycycline in 15 cases each,
Amoxycillin in 13cases, Paracetamol in 10 cases, Nevirapine in 9 cases,
Ciprofloxacin in 8 cases, Carbamezapine in 6 cases, Cefixime in 5 cases,
Diclofenac, penicillin and Ibuprofen in 4 cases each, Sodium valproate,
Piroxicam, Aspirin, Metronidazole & Nimesulide in 3 cases each. Tetracycline,
Chloroquine, Isoniazid & Cefoperazone in 2 cases each. Mefenemic acid,
Griseofulvin, Norfloxacin, Dapsone, Phenobarbitone, Imipramine, Imatinib
mesylate & Efavirenz each were incriminated in 1 case each.
9. Drugs and ACDRs caused by them:
Cotrimoxazole was found in 26 FDE cases, 5 cases of urticaria, 3 cases of
urticaria with angioedema, 1 case each of SJS and EMF. Phenytoin in 8 cases of
maculopapular rash , 5 cases of DRESS, 1 case of TEN, 1 case of SJS. Amoxycillin was seen in 9 cases of FDE, 1 case each of urticaria, SJS,
Erythroderma, Maculopapular rash.Nevirapine was implicated in 2 cases of
TEN, 3 cases of erythroderma,4 cases of maculopapular rash. Paracetamol was
seen in 2 cases each of FDE, urticaria, urticaria with angioedema & 1 case each
of TEN & EMF. Carbamezapine was seen in 2 cases each of FDE &
Erythroderma and in 1 case each of TEN & SJS .Cefixime was seen with 3 cases
of FDE, 1 case each of Urticaria, DRESS & maculopapular rash.Diclofenac
sodium & Ibuprofen were associated with 4 cases each of FDE. Sodium
valproate : 1 case of FDE, 2 cases of maculopapular rash, total of 3
cases. Piroxicam : 2 cases of FDE, a case of urticaria .
10. Site of involvement for common individual drugs:
Cotrimoxazole was the most common drug causing cutaneous in 12 and
both involvement in 15 cases, followed by doxycycline and phenytoin each in 6
cases of cutaneous and 9 cases of both. Amoxycillin in 6 cutaneous and both in
7 cases. Paracetamol in 6 cutaneous and both in 4 cases. Nevirapine in 3
cutaneous cases and 6 of both cases. Carbamezapine in 4 cutaneous and 2 case
of both. Ciprofloxacin in 7 cases of cutaneous and 1 case of both, Cefixime in 1
case of cutaneous and 4 cases of both, Diclofenac and Ibuprofen each in 2 cases
in both categories, Sodium valproate and Piroxicam each in 2 cases of cutaneous
and 1 case of both skin and mucosal involvement.
11. Associated diseases in ACDRs:
Maximum number of cases were seen with patients taking drugs for
underlying upper respiratory tract infections; 32 (19.63%), followed by seizure
disorders 24 (14.72%) cases, then followed by fever and headache 18 (11.04%)
cases, HIV was seen in 10 (6.13%) cases, equal no. of patients that is 9 (5.52%)
cases were seen for both lower respiratory tract infections and dental caries &
gingivitis. Among chronic long standing diseases Diabetes mellitus was seen in
7 (4.29%) cases, Hypertension was seen in 6(3.68%) cases, both diabetes and
hypertension were seen in 4 (2.4%) cases. Urinary tract infections were seen in
6 (3.68%) cases, 4 (2.4%) cases each of arthritis and bursitis & acute and chronic
suppurative otitis media were seen.
3 (1.84%) cases each of tuberculous meningitis, malaria, acute diarrhea, myalgia
& typhoid were seen. 2 (1.22%) cases of pyoderma were seen. Single cases each
of leprosy, depression, chronic lymphocytic leukemia, epididymoorchitis &
external hordeolum were seen.
12. Family history in ACDRs:
There was no positive family history in any of the cases.
CONCLUSION :
A total of 163 patients out of 1,03,536 were diagnosed with ACDRs. The
incidence of Cutaneous adverse drug reaction in this study was 0.15% during
this study period of 2 years.
Maximum number of the patients were in the 4thand 5th decade, closely
followed by patients in 1st and 3rd decades.Both the genders were almost equally
involved with a slight predominance of male patients.
Fixed drug eruption was the commonest type of ACDR followed by Urticaria
and Maculopapular rash, next closely followed by erythroderma .
Out of all the ACDRs 84 cases had exclusive cutaneous involvement only. Both
skin and mucosa were involved in rest of the 79 cases. Out of these 79 cases 47
had only oral mucosal involvement, 5 had genital mucosal involvement only and
27 had both the mucosa involved. Recurrent episodes were seen in 76 patients
of all the total cases.
The commonest class of drug causing ACDR was antimicrobials, among
these antimicrobials antibacterials were the commonest subclass involved. Non
steroidal anti-inflammatory drugs were the second commonest followed by
anticonvulsants. Other groups which caused ACDR were antidepressants and
cancer chemotherapy.
Amongst all the drugs Cotrimoxazole was the commonest drug causing
ACDR followed by equal involvement of phenytoin and doxycycline .
Among the individual ACDRs, FDE was most commonly caused by
Cotrimoxazole. Mucosal involvement was most commonly seen with
Cotrimoxazole followed by Phenytoin and doxycycline in succession. None of
the patients had a positive family history of drug reaction.
Upper respiratory tract infection was the most common underlying
systemic disorder following which patients had consumed the drug and
developed ACDR
