Indian Journal of Dermatology
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Year : 2005  |  Volume : 50  |  Issue : 3  |  Page : 146-149
Intertriginous drug eruptions

Department of Dermatology, Venereo1ogy & Leprosy, Indira Gandhi Medical College. Shimla, India

Correspondence Address:
Ramesh Chander Sharma
Department of Dermatology. Venereology & Leprosy, Indira Gandhi Medical College, Shimla 171 001
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Drug eruptions confined to intertriginous areas are rare and unusual cutaneus manifestations of amoxicillin sensitivity. We describe here three such cases of intertriginous drug eruptions. Two of these patients had developed fexural exanthematous rash and mild systemic symptoms following amoxicillin administration while in the third it was due to, hitherto unreported, celecoxib. Their possible patho-mechanism in the light of current knowledge is also discussed.

Keywords: Intertriginous drug eruptions, Flexural drug eruptions, Baboon syndrome, Celecoxib, Amoxicillin

How to cite this article:
Mahajan VK, Sharma RC. Intertriginous drug eruptions. Indian J Dermatol 2005;50:146-9

How to cite this URL:
Mahajan VK, Sharma RC. Intertriginous drug eruptions. Indian J Dermatol [serial online] 2005 [cited 2023 Jun 2];50:146-9. Available from:

   Introduction Top

Cutaneous drug eruptions are probably the most frequent of all manifestations of drug sensitivity. Most drugs are capable of causing several and different types of eruptions. The common morphologic patterns were exanthematous (39%), urticaria and /or angioedema (27%), fixed cutaneous eruption (16%) and erythema multiforme (5.4%). While 18% were of variable morphology.[1] Acneiform eruptions, erythema nodosum, pityriasis rosea-like and psoriasiform lesions are some of the milder drug eruptions while  Stevens-Johnson syndrome More Details, toxic epidermal necrolysis (TEN) and exfoliative dermatitis are more severe manifestations. Their pathomechanism is complex and clinical manifestations are due to chemical mediators like histamine, leukotrenes or prostaglandins released from sensitized tissue mast cells or circulating basophil leukocytes.

Eruptions confined to intertriginous areas and mimicking intertrigo are unusual forms of drug eruptions. We present here three cases of intertriginous drug eruptions and discuss their possible pathomechanism.

   Case reports Top

Case 1

This 45-year-old male, a patient of seropositive rheumatoid arthritis, was admitted with history of fever, burning micturition and generalised maculo-papular pruritic rash. History revealed that he had received celecoxib 200 mg twice daily for joint pain in the preceding three days. He was febrile (temp 39C) and cutaneous examination revealed generalised exanthematous. non-pustular eruptions and erythematous, circinate erosive, scaly plaques in both axillae and genitocrural folds. There was diffuse facial erythema and edema. Perimeatal and oropharyngeal mucous membranes were congested. Systemic examination did not reveal significant abnormality. Complete blood counts, blood sugar, liver and kidney function tests, serum uric acid, urinalysis. ECG. and chest X-ray were normal. KOH mounts of scrapings from genitocrural area did not demonstrate any yeast cells or fungus. A biopsy from the lesion showed necrotic keratinocytes, epidermal edema, basal cell degeneration and perivascular inflammatory cell infiltrate, features similar to TEN. With the possibility of drug induced eruptions, celecoxib was withdrawn and the rash cleared in a week's time with oral predinisolone 40mg/day for five days and antihistamines. Rechallenge performed two weeks later showed similar but milder rash with half the dose of celecoxib forcing discontinuation of procedure.

Case 2

This 5-year-old boy presented to us with generalised maculopapular rash and erythematous scaly lesions over circumoral area, anterior neckfold, axillae and groins. History revealed that the child had received amoxicillin for respiratory tract infection for three days prior to onset of cutaneous eruptions. He was uncomfortable, had chapping of lips, erythema and scaling of perioral region along with erythematous, scaly circinate plaques involving neckfold [Figure - 1], axillae and genitocrural areas in addition to generalised, non-pustular exanthematous rash. Systemic examination and routine laboratory investigations did not reveal any significant abnormality. KOH mounts from circinate lesions were negative for fungus.

Withdrawal of amoxicillin, and symptomatic treatment with antihistaminic drugs and topical emollients resulted in clearance of rash in about 5 days.

Case 3

This 21/2-year-old female child had developed acute urticarial rash with angioedema and erythematous, circinate, scaly eruptions in the neckfold, axillae and genitocrural areas following administration of amoxicillin for two days, prescribed for upper respiratory tract infection. She also had urticarial wheals all over the body but no pustular lesions. There was also conjuctival congestion and stomatitis. KOH mounts from groins and neck lesions did not reveal fungus.

Treatment with antihistamines and withdrawal of amoxicillin cleared the eruption in 2-3 days.

   Discussion Top

The clinical appearance of a drug reaction is usually of little help in determining the offending drug or the pathogenetic mechanism involved. A temporal correlation between drug administration and onset of rash provides circumstantial but a strong evidence of the drug being the cause. All our three patients had received the offending drugs for 2-4 days prior to onset of their very unusual cutaneous eruptions. As a matter of fact we did not suspect these cases to be of drug eruptions at first instance. They might have passed off as cases of intertrigo, had the cutaneus lesions been not associated with generalised exanthem, mucosal congestion, mild systemic toxic symptoms and their subsidence after withdrawal of the suspected drugs.

Urticaria, morbilliform or maculopapular rash occur in 1-2% treatment courses with amoxicillin.[2] Other than occasional case reports of intertriginous eruptions,[3],[4] fixed drug eruptions, recurrent localised pustulosis and acute generalised exanthematous pustulosis (AGEP) due to amoxicillin have often been reported.[5],[7] Celecoxib, a cox-2 antagonist, has been reported to cause erythema multiforme, Stevens-Johnson syndrome, fixed drug eruptions, severe maculopapular exanthem and even anaphylactoid reaction.[8] Our

case-1 having intertriginous drug rash due to celecoxib is first of its kind.

Cutaneous reactions can arise either by activation of host immunologic pathways or by non-immunologic mechanisms. Although, we failed to speculate the mechanism involved in localisation and pathogenesis of these intertriginous drug eruptions in our patients; they appear to be of immunologic origin. In immunogenic reactions different subsets of T-cell population appear to be activated by drug-tissue macromolecular complex via antigen presenting cells and mediating a different clinical reaction. For instance, Th- I type of T-cell activation causes production of IF-g and IL-2 which may result in morbilliform drug rash, contact dermatitis, or perhaps TEN[9]. Similarly activation of Th2 cells produces IL4. IL5. IL13 which in turn causes IgE antibody production leading to clinical reactions such as urticaria or anphylaxis.[9] The IgE dependant drug reactions are more common with penicillins including amoxicillin. Celecoxib, like other NSAIDS, too, probably interferes with prostaglandin synthesis from arachidonic acid resulting in excess cytokine production and is perhaps responsible for morbilliform rash, contact dermatitis or TEN like features.

Localisation of these eruptions is also interesting. The reason for their flexural predilection is not clear. Occlusion, heat and sweating in body folds perhaps contribute in their localisation to some extent.[10] The rash of AGEP involving flexural aspects is characterised by numerous non-follicular pustules.[11] This rare but well recognised drug hypersensitivity reaction in most cases is due to antibiotics including b lactum and macrolides, isoniazid, cytarabrine and various chemotherapeutic regimens.[12] Absence of pathognomic non-follicular pustules in all our cases make them different from AGEP. Such flexural involvement also resembles "baboon syndrome". This term has been used to describe both a drug rash as well as systemic allergic contact dermatitis characteristically involving buttocks, upper-inner thighs and axillae. Amoxicillin, ampicillin, nickel, heparin and mercury are well known to provoke it.[2] lt is possible that celecoxib too is able to elicit such a phenomenon.

Routine laboratory investigations are not diagnostic and other tests such as peripheral eosinophilia, in-vitro lymphocyte toxicity, intradermal and patch testing and lymphocyte proliferation test have limited clinical use. The challenge tests too are open to misinterpretation.[13] Therefore, the diagnosis is mainly on high clinical suspicion and is often an assessment of probability. Apart from their documentation an early clinical diagnosis and appropriate management (withdrawal of offending drug) of such unusual drug eruptions of acute onset is of practical importance.

We agree with the views of Wolf et al that such eruptions may not be rare and are probably overlooked or misdiagnosed as their presentations are often baffling to the unsuspecting clinician. Furthermore, consensus needs to be arrived at to describe such uncommon drug eruptions under the heading 'flexural drug eruptions" as suggested by Wakelin et al for their uniform classification and documentation.

   References Top

1.Stern RS, Wintroub BU. Cutaneous reaction to drugs. In: Freedbrug IM, Eisen AZ, Wolff K, Asten KF Goldsmith LA, Katz SI, Fitzpatrick TB, eds. Dermatology in General Medicine. 5th edn. New York McGraw Hill, 1999:1633-42.  Back to cited text no. 1    
2.Breathnach SM. Drug reactions. In: Champion RH, Burton JL, Burns DA. Breathnach SM, eds. Textbook of Dermatology. 6th edn. Oxford Blackwell Science Ltd, 1998: 3349-517.  Back to cited text no. 2    
3.Wolf R, Brenner S, Krakowski A. lntertriginous drug eruption. Acta Dermatol Venereol 1992 ; 72: 441-2.  Back to cited text no. 3    
4.Wakelin SH, Sidhu S, Orton Dl, Chia Y, Shaw S. Amoxycillin-induced flexural exanthema. Clin Exp Dermatol 1999; 24: 7l-3.  Back to cited text no. 4    
5.Chowdhury FH. Fixed genital drug eruption. Practical Med 1982; 226:1450.  Back to cited text no. 5    
6.Shuttleworth D. A localised, recurrent pustular eruption following amoxycillin administration. Clin Exp Dermatol 1989;14:367-8.  Back to cited text no. 6    
7.Roujeau JC. Bioulac-sage P, Boursean C, et al. Acute generalised exanthematous pustulosis, analysis of 63 cases. Arch Dermatol 1991; 127: 1333-8.  Back to cited text no. 7    
8.Hempel M, Bircher AJ. Hypersensitivity to celecoxib: the variety of adverse reactions. Dermatology 2002;205-8.  Back to cited text no. 8    
9.Merk HF. Hertl M. Immunologic mechanisms of cutaneous drug reactions. Semin Cutan Med Surg 1996;15:228-35.  Back to cited text no. 9    
10.Anderson KE, Hjorth N, Nienne T. The baboon syndrome: systemically induced allergic contact dermatitis. Contact Dermatitis 1984 ; 10: 97-100.  Back to cited text no. 10    
11.Sidoroff A, Halevy S, Bavinck JNB, Vaillant L, Roujeau JC. Acute generalised exanthematous pustulosis (AGEP)- A clinical reaction pattern. J Cutan Pathol 2001 ; 28:113-9.  Back to cited text no. 11    
12.Chin A, Kohler S, McGuire J, Kimball AB. Cytarabrine induced acute generalised exanthematous pustulosis. J Am Acad Dermatol 2002; 45: 633-5.  Back to cited text no. 12    
13.Girard M. Oral provocation: limitations. Semin Dermatol 1989; 8:192-5.  Back to cited text no. 13    


[Figure - 1]


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