3/24/2015 ACETAMINOPHEN­INDUCED CELLULITIS­LIKE FIXED DRUG ERUPTION

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Indian J Dermatol. 2011 Mar­Apr; 56(2): 206–208.doi: 10.4103/0019­5154.80419

PMCID: PMC3108524

ACETAMINOPHEN­INDUCED CELLULITIS­LIKE FIXED DRUG ERUPTIONNeila Fathallah, Chaker Ben Salem, Raoudha Slim, Lobna Boussofara, Najet Ghariani, and Kamel Bouraoui

Department of Clinical Pharmacology, Faculty of Medicine of Sousse, Sousse, TunisiaDepartment of Dermatology, Farhat Hached University Hospital, Sousse, TunisiaAddress for correspondence: Neila Fathallah, Ave Mohamed Karoui, 4002 Sousse, Tunisia. E­mail: neilafathallah@gmail.com

Received 2009 Aug; Accepted 2010 Jul.

Copyright © Indian Journal of Dermatology

This is an open­access article distributed under the terms of the Creative Commons Attribution­Noncommercial­Share Alike 3.0 Unported, which permitsunrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Acetaminophen is a widely used analgesic drug. Its adverse reactions are rare but severe. An 89­year­old mandeveloped an indurated edematous and erythematous plaque on his left arm 1 day after acetaminophen ingestion.Cellulitis was suspected and antibiotictherapy was started but there was no improvement of the rash; there was aspectacular extension of the lesion with occurrence of flaccid vesicles and blisters in the affected sites. Thediagnosis of generalized­bullous­fixed drug eruption induced by acetaminophen was considered especially with areported history of a previous milder reaction occurring in the same site. Acetaminophen was withdrawn and therash improved significantly. According to the Naranjo probability scale, the eruption experienced by the patientwas probably due to acetaminophen. Clinicians should be aware of the ability of acetaminophen to induce fixeddrug eruption that may clinically take several aspects and may be misdiagnosed.

Keywords: Acetaminophen, generalized bullous fixed drug eruption, cellulitis

Introduction

Acetaminophen is among the most commonly prescribed medications.[1] Its cutaneous adverse effects are rare,varying from transient pruritis or maculopapular rash to Stevens–Johnson syndrome and even fatal toxic epidermalnecrolysis.[2,3] Only few cases of acetaminophen­induced generalized­bullous fixed drug eruption have beenreported in literature.[4,5] We report a case of generalized­bullous­fixed drug eruption induced by acetaminophenand presenting initially like cellulitis.

Case Report

An 89­year­old man presented with a one­day history of painful erythematous and edematous eruption affecting hisleft arm.

The patient's medical history was significant for hypertension treated with furosemide (40 mg/day). Moreover, therewas a notion of self­medication by acetaminophen for recent arthralgia in the latest 48 h.

On physical examination, the patient was febrile with an axillar temperature of 39 C. He had also a wet cough withexpectorations of thick yellowish sputum. Vital signs were within normal range. His left arm was red, glossy, andwarm to the touch. The plaque was tender and indurated with definite borders, covering the left forearm andextending to the upper arm [Figure 1]. Clinically, the lesion's aspect mimicked a cellulites, and the patient wasinitially treated with intravenous cefapirine (4 g/day).

Performing your original search, cellulitis journal, in PMC will retrieve 7347 records.

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3/24/2015 ACETAMINOPHEN­INDUCED CELLULITIS­LIKE FIXED DRUG ERUPTION

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Figure 1On the left thigh, two superficial blisters and a ruptured bulla roof are seen on an erythematousbase with epidermal detachment: generalized­bullous­fixed drug eruption

Laboratory investigations showed the following values: white blood cell count of 8.3×10 /L (normal range, 4.5–11×10 /l); hemoglobin 16 g/dl (normal range, 12–16 g/dl); blood urea nitrogen 9.6mg/dl (normal range, 6–21mg/dl); and a creatinine level of 1.6 mg/dl (normal range, 0.5–1.3 mg/dl).

Two days later, superficial flaccid blisters appeared at the affected site and a varying size of multiple well­circumscribed erythematous and hyperpigmented patches were observed on the right arm, the abdomen, and bothlegs. Some of them were studded with flaccid vesicles and blisters [Figure 2]. The mucous membranes and the facewere not involved.

Figure 2A large erythematous, edematous, and shiny plaque with determinateborders covering the left arm: Cellulitis­like fixed drug eruption

In view of this skin disorder, the diagnosis of generalized­bullous­fixed drug eruption and Stevens–Johnsonsyndrome were considered.

Meanwhile, the patient gave history of similar but a more localized reaction following acetaminophen ingestionoccurring 2 years earlier. A skin biopsy was carried out. Histopathological examination of the lesional biopsyspecimen taken from a flaccid blister overlying a purplish­livid patch on the left arm revealed a thin epidermis withnecrosis of epidermal keratinocytes. The dermis was edematous with a mixed inflammatory infiltrate consisting ofmononuclear cells and few eosinophils. Direct immunofluorescence revealed no IgG, IgE, or IgA and C3deposition at the basement membrane zone.

The diagnosis of acetaminophen­induced generalized­bullous­fixed drug eruption was confirmed based on theclinical and histological findings. Acetaminophen was then withdrawn. The blisters and vesicles disappeared fewdays later.

Discussion

Fixed drug eruption is a specific cutaneous adverse reaction induced by an ever­expanding list of drugs. It usuallyconsists of solitary or multiple lesions occurring after the drug exposure. The reactions vary in severity fromlocalized lesions to generalized eruptions. Acetaminophen­induced fixed drug eruption is reported in literature inless than 1.5% of all cases of fixed drug eruption.[6] This adverse reaction rarely progresses to a generalizedbullous fixed drug eruption. It can exceptionally appear under a clinical shape, which mimes cellulitis.[7] In ourreview of the literature and according to data from a MEDLINE search for over the past 40 years, we identifiedonly one publication regarding a case of cellulitis­like fixed drug eruption induced by acetaminophen. In this case,the fixed drug eruption, which was developed in a 65­year­old woman clinically seemed like cellulitis. There wasabsence of development of blisters even after rechallenge of acetaminophen.[7]

Our case is original in the sense that the eruption took several aspects in the same patient and changed from acellulitis­like eruption to a generalized­bullous one. In fact, our patient developed at first an eruption clinicallymimicking cellulitis and initially treated as such. However, the exacerbation of clinical manifestation underantibiotictherapy and with continued exposure to acetaminophen suggested the diagnosis of fixed drug eruptionespecially with the reported history of a previous milder reaction occurring in the same site. The clinical aspect ofthe eruption with the flaccid vesicles and blisters was unusual in fixed drug eruption. After a repeated exposure tothe offending drug, the severity of fixed drug eruption may increase and may progress rarely to a generalizedbullous­fixed drug eruption, which is an extensive form of fixed drug eruption. It is characterized by multiple, large,

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well­defined, purplish­livid patches eroded by flaccid blisters.[8] The clinical aspect may be misdiagnosed asStevens–Johnson syndrome, which is an important differential diagnosis that can be separated by clinical means,but not in terms of the histopathology. In generalized­bullous­fixed drug eruption, lesions occur quite early withinfew hours of drug intake. It generally involves the same sites, which were affected in the previous episodes. Bycontrast, recurrent lesions in Stevens–Johnson syndrome show no predilection for previously affected sites. Theepidermal changes in generalized­bullous­fixed drug eruption and Stevens–Johnson syndrome vary from fewscattered necrotic keratinocytes to full thickness epidermal necrosis and the histopathological differentiation cannotbe easily distinguished in all conditions. In fixed drug eruption, a mixed inflammatory infiltrate is noted aroundsuperficial and deep plexuses, which mainly contain neutrophilis and eosinophilis in addition to lymphocytes andhistocytes. Presence of intraepidermal vesiculation with keratinocyte necrosis makes the diagnosis of fixed drugeruption more likely.[9]

In our case, there are many arguments in favor of generalized­bullous­fixed drug eruption induced byacetaminophen. In fact, there is a temporal correlation between the drug introduction and the rash appearance,previous history of milder reaction, favorable evolution and rapid recovery after acetaminophen withdrawal. Skinbiopsy was also consistent with this diagnosis. According to the objective causality assessment by the Naranjoprobability scale,[10] acetaminophen­induced bullous­fixed drug eruption was probable.The patient was firmlyinstructed to avoid self­medication, particularly with acetaminophen.

Conclusions

Physicians should be aware of the risk of the occurrence of cutaneous adverse reactions under acetaminophen,especially fixed drug eruption that may clinically appear with variable aspects and may be misdiagnosed.

Footnotes

Source of Support: Nil

Conflict of Interest: Nil.

References

1. García Domínguez MD, Lucena González MI, Ramírez Torres JM, Andrade Bellido RJ, Sánchez de la CuestaF. Drug use pattern in an ambulatory geriatric population. Rev Clin Esp. 1992;191:412–5. [PubMed]

2. Wohl Y, Goldberg I, Sharazi I, Brenner S. A case of paracetamol­induced acute generalized exanthematouspustulosis in a pregnant woman localized in the neck region. Skinmed. 2004;3:47–9. [PubMed]

3. Halevi A, Ben­Amitai D, Garty BZ. Toxic epidermal necrolysis associated with acetaminophen ingestion. AnnPharmacother. 2000;34:32–4. [PubMed]

4. Ayala F, Nino M, Ayala F, Balato N. Bullous fixed drug eruption induced by paracetamol: Report of a case.Dermatitis. 2006;17:160. [PubMed]

5. Hern S, Harman K, Clement M, Black MM. Bullous fixed drug eruption due to paracetamol with an unusualimmunofluorescence pattern. Br J Dermatol. 1998;139:1129–31. [PubMed]

6. Ozkaya­Bayazit E, Bayazit H, Ozarmagan G. Drug related clinical pattern in fixed drug eruption. Eur JDermatol. 2000;10:288–91. [PubMed]

7. Prabhu MM, Prabhu S, Mishra P, Palaian S. Cellulitis­like fixed drug eruption attributed to paracetamol(acetaminophen) Dermatol Online J. 2005;11:24. [PubMed]

8. Ada S, Yilmaz S. Ciprofloxacin­induced generalized bullous fixed drug eruption. In J Dermatol VenereolLeprol. 2008;74:511–2. [PubMed]

9. Lin TK, Hsu MM, Lee JY. Clinical resemblance of widespread bullous fixed drug eruption to Stevens­Johnsonsyndrome or toxic epidermal necrolysis: report of two cases. J Formos Med Assoc. 2002;101:572–6. [PubMed]

10. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probabilityof adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–45. [PubMed]

3/24/2015 ACETAMINOPHEN­INDUCED CELLULITIS­LIKE FIXED DRUG ERUPTION

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108524/ 4/4

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