Kumaran Sendhil , Sandhu Kamaldeep , Saikia Uma Nahar , Handa Sanjeev

Bioline International

Indian J Dermatol Venereol Leprol January-February 2004 Vol 70 Issue 1 44Serum sickness classically refers to a systemicimmunological reaction caused by injected serum andoccurs due to deposition of an antigen-antibody-complement complex. It occurs when an antigen (i.e.serum) persists in the circulation for a long durationstimulating IgG or IgM antibody synthesis. Theseantibodies, along with complement, form complexeswhich are deposited in various organs. Themanifestations develop according to the organinvolved. Since heterologous serum is rarely used, sucha systemic reaction due to serum is rare. Other causeslike drugs are now more commonly implicated and theresultant reaction is called a serum sickness likereaction. Minocycline can cause such a reaction rarely.2,3Our patient had all the features of serum sickness likereaction, namely angioedema, lymphadenopathy,arthralgia and fever. It is interesting to note that like mostprevious reports our patient was also female. Althoughthere may be hematological alterations likehypocomplementemia or signs of renal impairment, theirabsence does not exclude this diagnosis and acombination of clinical signs is sufficient for the diagnosisof SSLR. Such a reaction should be recognized at theearliest and the drug should be stopped. We hope thisreport helps to increase awareness about this rare adverseeffect of minocycline, which is being used increasinglycommonly for the treatment of acne in India.Nilendu Sarma, Subrata Malakar,Koushik Lahiri, Uttam BanerjeeRita Skin Foundation, Kolkata, India.Address for correspondence:  Dr. Nilendu Sarma, Rita SkinFoundation, GD 381, Salt Lake, Kolkata - 700106. India.E-mail: nilendusarma@yahoo.co.inREFERENCES1. Strauss AS, Thiboutot DM. Disease of the sebaceous glands.In: Freedberg IM, Eisen AZ, Wolff K, et al, editors. Dermatologyin general medicine. 5th ed. New York: McGraw-Hill; 1999. p.769-784.2. Puyana J, Urena V, Quirce S, Fernandez-Rivas M, Cuevas M,Fraj J. Serum-sickness-like syndrome associated withminocycline therapy. Allergy 1990;45:313-5.3. Malakar S, Dhar S, Malakar RS. Is serum sickness an uncommonadverse effect of minocycline treatment? Arch Dermatol2001;137:100-1.Nimesulide induced bullous fixed drugeruption of the labial mucosaSir,A fixed drug eruption (FDE) is a distinct drug inducedreaction pattern that characteristically recurs at thesame skin or mucosal site. We report a case of bullousFDE confined to the labial mucosa following intake ofnimesulide, a commonly used nonsteroidal anti-inflammatory drug in India.A 23-year-old man presented with multiple oral blistersof one day’s duration associated with marked burningand soreness. He had developed the lesions within 5to 6 hours of taking a single tablet of nimesulide (whichhe had taken by himself). He had also been takingroxithromycin for three days which had been prescribedfor his sore throat by an otolaryngologist. In the pasthe had taken multiple courses of roxithromycin for hisrecurrent sore throat without any complaints, but thiswas the first time that he had taken nimesulide.The patient was afebrile and there were no otherassociated systemic complaints. Examination revealedmultiple, tense bullae filled with clear fluid, varying insize from 0.5-1.5 cm, distributed over the upper labialmucosa with slight surrounding erythema (Figure 1).The rest of the oral mucosa and other mucosal siteswere free of lesions.A biopsy from the bullae was taken. HistopathologicalFigure 1: Bullous FDE lesions involving the labial mucosaLetters to EditorIndian J Dermatol Venereol Leprol January-February 2004 Vol 70 Issue 145examination revealed necrotic keratinocytes and amarked inflammatory infiltrate in the dermis, findingsconsistent with a fixed drug eruption.The patient was asked to stop both the drugs and toavoid nimesulide in the future. He was given a shortcourse of steroids in a tapering dose for two weeksfollowing which the lesions improved. The lesionshealed with mucosal hyperpigmentation.Brocq first introduced the term fixed drug eruption in1894.1 The pathogenetic mechanism underlying FDEis still enigmatic. The most commonly acceptedhypothesis is persistence of memory T cells in theaffected skin.2 CD8+ cells phenotypically resemblingeffector memory T cells have been shown to be greatlyenhanced in the lesions of FDE.3 The lesions of FDEusually start as an erythematous macule thatsubsequently evolves into a plaque. Vesicles and bullaedevelop at a later stage and are usually hemorrhagic.The lesions can occur on any part of the skin andmucous membranes. The sites of predilection are thelimbs, sacral region, genitalia, palmar and plantar skin.The oral mucosa may be involved in association withskin lesions or alone.The drugs that commonly cause mucosal FDE includeco-trimoxazole, oxyphenbutazone, and tetracycline.4Classically the transitional epithelium of themucocutaneous junctions is involved but strictlocalization of the lesion to the labial mucosa, as wasseen in our patient, is unusual. Systemic manifestationsare uncommon and include fever, malaise, nausea,diarrhea, abdominal pain, urethritis, and conjunctivitis.Nimesulide is a nonsteroidal anti-inflammatory agentwith antipyretic and analgesic properties. It is beingcommonly prescribed in India.5 Some of the side effectsreported with its use are pruritus, urticaria, purpura,maculopapular rash and localized toxic pustuloderma.6-7Due to severe hepatotoxicity and hemolytic anemiaassociated with its use, nimesulide is likely to bewithdrawn from the market in many countries.8To the best of our knowledge only 8 cases of FDEsecondary to nimesulide have been reported9-12 andthere is only one other report with primarily oralmucosal involvement.9  This report emphasizes anuncommon mucosal localization of bullous FDE due tonimesulide.Sendhil Kumaran, Kamaldeep Sandhu,Uma Nahar Saikia,* Sanjeev HandaDepar tments of Dermat ology, Venereology & Leprology and*Pathology, Post graduate Institute of Medical Education andResearch, Sector 12, Chandigarh. India.Address for correspondence: Dr. Sanjeev Handa, AssistantProfessor, Depar tment of Dermatology, Venereology andLeprology, Post Graduate Institute of Medical Education andResearch, Chandigarh - 160012, India.E-mail: handa_sanjeev@yahoo.comREFERENCES1. Brocq I. Eruption erythemato-pigmentee fixe due al’antipyrine. Ann Dermatol Venereol. 1894;5:308-13. Quotedfrom: Shiohara T, Nickoloff BJ, Sagawa Y, Gomi T, NagashimaM. Fixed drug eruption. Expression of epidermal keratinocyteintercellular adhesion molecule-1 (ICAM-1). Arch Dermatol1989;125:1371-6.2. Shiohara T, Nickoloff BJ, Sagawa Y, Gomi T, Nagashima M. Fixeddrug eruption. Expression of epidermal keratinocyteintercellular adhesion molecule-1 (ICAM-1). Arch Dermatol1989;125:1371-6.3. Shiohara T, Mizukawa Y, Teraki Y. Pathophysiology of fixeddrug eruption: the role of skin resident T cells. Curr OpinAllergy Clin Immunol 2002;4:317-23.4. Bhargava NC, Singh G. Fixed drug eruption due to twounrelated drugs: oxyphenbutazone and tetracycline. Int JDermatol 1981;20:435.5. Malhotra S, Pandhi P. Analgesics for pediatric use. Indian JPediatics 2000;67:589-90.6. Kanwar AJ, Kaur S, Thami GP. Nimesulide induced purpura.Dermatology 2000;201:326.7. Lateo S, Boffa MJ. Localised toxic pustuloderma associatedwith nimesulide therapy confirmed by patch testing. Br JDermatol 2002;147:624-5.8. Saha K. Use of nimesulide in Indian children must be stopped.BMJ 2003;326:713.9. Valsecchi R , Reseghetti A, Cainelli T. Bullous and erosivestomatitis induced by nimesulide. Dermatology 1992;185:74-5.10. Corderio MR, Gonacalo M, Fernandes B, Oliveira H, FiguedoA. Positive lesional patch tests in fixed drug eruption fromnimesulide. Contact Dermatitis 2000;43:307.11. Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED).Cutaneous reactions to analgesics, antipyretics and NSAIDS.Dermatology 1993;186:1641-69.12. Sarkar R, Kaur C, Kanwar AJ. Extensive fixed drug eruptionsto nimesulide with cross reactivity to sulphonamide in a child.Pediatr Dermatol 2002;19:553-4.Letters to Editor

Nimesulide induced bullous fixed drug eruption of the labial mucosa

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