Indian Journal of Dermatology
ORIGINAL ARTICLE
Year
: 2006  |  Volume : 51  |  Issue : 3  |  Page : 189--191

Cutaneous reactions due to antihypertensive drugs


JB Upadhayai1, Anup Kumar Nangia1, RD Mukhija1, Mukum Misra2, Lalit Mohan1, KK Singh1,  
1 Department of Skin & VD, Institute of BRD Medical College, Gorakhpur - 273 013, UP, India
2 Department of Medicine, Institute of BRD Medical College, Gorakhpur - 273 013, UP, India

Correspondence Address:
Anup Kumar Nangia
Department of Skin & VD, BRD Medical College, Gorakhpur
India

Abstract

Out of a total of 1147 patients on antihypertensive drugs, 23 (2.04%) developed adverse cutaneous drug reactions (ACDR). The commonest antihypertensive drug group causing ACDR was beta-blockers of which atenolol was the commonest culprit. The second most common group was calcium channel blockers with amlodipine as the commonest offender. The most common patterns of ACDR observed included urticaria followed by lichenoid drug eruption (LDE). We noted 2 new patterns of reactions; (i) one patient developed brownish blue pigmentation of nails while on atenolol for 3 years, which resolved in 4 months after withdrawal and (ii) another patient on amlodipine for 8 years developed Schamberg«SQ»s like purpuric pigmentation, which resolved on withdrawal of drug within 3 months. These findings have not been reported in the literature earlier. This study is presented for paucity of Indian data on ACDR due to antihypertensive drugs, and remarkable advancement in area of cardiovascular and antihypertensive pharmacology and a large number of population taking antihypertensive drugs.



How to cite this article:
Upadhayai J B, Nangia AK, Mukhija R D, Misra M, Mohan L, Singh K K. Cutaneous reactions due to antihypertensive drugs.Indian J Dermatol 2006;51:189-191


How to cite this URL:
Upadhayai J B, Nangia AK, Mukhija R D, Misra M, Mohan L, Singh K K. Cutaneous reactions due to antihypertensive drugs. Indian J Dermatol [serial online] 2006 [cited 2020 May 31 ];51:189-191
Available from: http://www.e-ijd.org/text.asp?2006/51/3/189/27982


Full Text

 Introduction



An adverse cutaneous drug reaction (ACDR) is an undesirable or unintended change in structure or function of the skin or its appendages, and mucous membrane while on medication. Adverse drug reactions are said to be the inevitable price we pay for the benefits of modern drug therapy. It is difficult to obtain reliable information on the incidence of drug reactions, possibly because of lack of standardized coding for drug reactions.

There is a large number of population on one or other antihypertensive drug. With the widespread use of these agents now-a-days, especially newer drugs, reports of ACDRs have increased enormously. However, pre-marketing clinical trials conducted before a new drug is licensed do not identify ACDR occurring in less than 0.1 to 1% of patients, or those occurring only after prolonged administration or with long latent period or occurring only in susceptible patients or those occurring when the drug is combined with other factors/drugs.

In view of large patients receiving antihypertensive agents and absence of any study from India except sporadic case reports, we evaluated the incidence and clinical profile of ACDR due to antihypertensive drugs.

 Materials and Methods



The study was carried out in the Department of Dermatology, BRD Medical College, Gorakhpur from January 2002 to May 2003. The study group consisted of all hypertensive patients taking antihypertensive drugs, attending the cardiology unit of Department of Medicine. All the patients on antihypertensive drugs who developed skin lesions were evaluated in the Department of Dermatology.

The patients in whom there was no improvement within 6 months after withdrawal of antihypertensive drug, were excluded from the study. In patients with ACDR possibly due to other concomitantly administered drugs, confirmation was done by provocative tests.

After confirmation of the reaction as drug reaction, we searched for the causative drug among the antihypertensives (by clinical evaluation, skin biopsy and provocative tests). Oral challenge test is the gold standard for the diagnosis of ACDR. This test was done after 6 weeks of subsidence of lesions following withdrawal of the offending drug. The schedule of this test is as follows: ¼ dose on day one, if no reaction ½ dose on day 2, even if no reaction then full dose on day 3. Even if no reaction occurred, the daily full dose was given for one week. If no reaction occurred, the test was considered negative and next suspected drug was tested in the same manner.

The patch test (topical provocation test) is a safe alternative to oral challenge test. The test was done 6 weeks after complete subsidence of eruptions. White petrolatum was used as vehicle. Drug was used in the concentration of 1 and 10%. Upper back was preferred for patch testing. The patches were removed after 2 days and read on 2nd and 4th day. The reaction on 4th day was regarded as conclusive.

Observations

A total of 1986 patients attended the cardiology out patients department (from July 2002 to August 2003) of which 1147 were on antihypertensive drugs. Fifty-four (54) patients had one or other type of skin reactions. Thirty-one patients were excluded fromt he study (22 did not improve on withdrawal and 9 patients dropped out). The remaining 23 patients who improved on withdrawal of drugs were included. These were studied further.

Out of these 23 patients skin biopsy was done in 6, 12 were tested with oral challenge test and 4 patients underwent patch test; 7 patients refused to undergo challenge test or biopsy.

The male female ratio was 1.09: 1 and mean age of patients was 52 ± 12 years: The age difference between male and female and their ratio were not significant. Maximum number of patients 7 (30.43%) were in 37-46 year age group which is followed by 6 (26.29%) in 64-73 year age group.

Maximum number of patients with ACDR was seen with atenolol followed by amlodipine. The most common type of ACDR was found to be urticaria followed by Lichenoid drug eruption (LDE) [Table 1]. The average latent period for urticaria was 38.93 days and for LDE 19.6 months. Psoriasiform eruptions appeared after 2 years of exposure, while maculopapular eruption occurred after 17.5 days and vasculitis after 28.75 days [Table 2].

Oral challenge test was positive in 8 out of 12 patients (66.67%) [Table 3]. The ACDR where latent period was longer showed positive oral challenge test on full dose for longer duration, and where latent period was short showed positive oral challenge test with lower dose of drug within 1 day. Six patients were subjected to histopathological examination of which 2 were conclusive and 4 were non-conclusive.

Four patients were patch tested; only one patient showed equivocal results and other 3 were negative.

 Discussion



In our study, the incidence of ACDR was 2.04%. No exact incidence of ACDR from antihypertensive drugs is available in literature. However, Danish National Board of Health's Committee on adverse drug reactions (ADR) showed that 10-60% of adverse drug reactions from antihypertensive drugs were dermatological.[1] The combination of amiloride (5 mg) and hydrochlorothiazide (50 mg) had the highest number of recorded ADR; 59% of these were in the skin.[1] One recent study from Manipal, India shows 3.75% ACDR due to cardioactive drugs, urticarial patterns of drug eruptions were excluded in the study.[2]

In our study, male: female ratio and age difference between male and female was not significant. This may be because of the fact that prevalence of hypertension does not show gender bias.

The commonest antihypertensive drug group causing ACDR was beta-blockers in which atenolol was the most common offender. Second most common group of antihypertensives was calcium channel blockers with amlodipine being the commonest offending drug. All the groups of antihypertensive drugs have been documented to show ACDR in earlier studies.[3],[4],[5],[6]

In our study the commonest ACDR was urticaria with the most common causative agent being amlodipine. The latent period for urticaria was 3 days to 3 months, while the resolution time was 4-14 days. Earlier workers have published similar observations.[7]

LDE was the second common ACDR mostly caused by atenolol. Latent period for LDE ranged from 1 to 24 months (19.6 months average) and the resolution time was 1 to 4 months. These observations are similar to a study of 17 patients with LDE by Halevy and Shai.[8]

We observed an interesting finding in a patient on atenolol for 3 years; he developed brownish blue pigmentation of nails, which resolved in 4 months after drug withdrawal. This observation has not been mentioned earlier in literature with atenolol, but has the reported with timolol, a beta-blocker, which was reported to cause brownish pigmentation of nails.[9]

Another interesting observation was in a patient on amlodipine for 8 years developing Schamberg's like purpuric pigmentation with ankle oedema, which resolved on withdrawal of amlodipine within 3 months. the probable explanation of Schamberg's like purpuric pigmentation could be prolonged ankle eema caused by amlodipine, which may damage the normal permeability of capillaries, thus causing subacute or chronic capillaritis, producing purpuric pigmentation.

 Conclusion



As a large number of population is receiving antihypertensive drugs, proper awareness of ACDR is necessary for every physician for early diagnosis and better management of ACDR due to antihypertensive drugs.

References

1Thestrup-Pedersen K. Adverse reactions in skin from antihypertensive drugs. Dan Med Bull 1987;34:3-5.
2Sehgal S, Balachandran C, Shenai SD. Clinical study of cutaneous drug reactions in 80 patietns. Indian J Dermatol Venerol Leprol 2003;69:6-7.
3Bolzano K, Arriaga J and Bernal R. The antihypertensive effect of lisinopril compared to atenolol in patients with mild to moderate hypertension. J Cardiovasc Pharmacol 1997;9:543-7.
4Kitamura K, Kanasashi M, Suga C, Saito S, Yoshida S, Ikezawa Z. Cutaneous reactions induced by calciumchannel blocker: High frequency of psoriasiform eruptions. J Dermatol 1993;20:279-89.
5Stephen SA. Unwanted effect of propranolol. Am J Cardiol 1966;18:463-72.
6Stern R, Khalsa JH. Cutaneous adverse reactions: Association with calcium channel blockers. Arch Intern Med 1989;149:829-32.
7Sabroe RA, Kobza Black A. Angiotensin converting enzyme (ACE) inhibitors and angioedema. Br J Dermatol 1997;136:153-8.
8Halevy S, Shai A. Lichenoid drug eruption. J Am Acad Dermatol 1993;29:249-55.
9Runne U, Orfando CE. The human nail: Structure, growth and pathological changes. Curr Prob Dermatol 1981;9:102-49.