Bullous Fixed Drug Eruption Probably Induced by Paracetamol

Abstract

We report a case of a 42-year-old male who presented with second episode of bullous eruptions after ingestion of paracetamol. There were no systemic complaints. The temporal correlation with the drug, history of a similar episode and the quick improvement led us to a diagnosis of bullous fixed drug due to paracetamol. Applying Naranjo's algorithm, a causality score of 8 was obtained and was categorized as probable reaction to paracetamol. Clinicians should be vigilant of the possible adverse reactions to drugs with robust safety profiles. Drug alert cards could play an important role in preventing recurrences.

Introduction

What was known?

Fixed drug eruptions (FDEs) is an entity that is frequently encountered by all physicians. They are clinically distinct with characteristic recurrences at the same sites on re-exposure to offending drug. Only a few cases of paracetamol-related bullous FDE have been reported.

Cutaneous skin reactions are common. Recent studies from India suggest that fixed drug eruptions (FDEs) account for 20–43% of all cutaneous adverse drug reaction (CADR) patterns.[1,2] Exact pathogenesis remains obscure but intraepidermal CD8⁺ T cells that persist at the previous injury site mediate and are directly implicated in the epidermal injury causing localized cutaneous changes.[3] FDE has multiple variants, including generalized, linear, bullous, urticarial, pigmenting, nonpigmenting, wandering, eczematous, psoriasiform, erythema dyschromicum perstans like, vulvitis and oral FDE.[4,5,6,7] Still rarer variants are FDE presenting as acute paronychia and that mimicking parapsoriasis.[8,9]

Case Report

A 42-year-old man presented to our dermatology clinic with painful blistering eruption affecting the acral sites and lips. The day before, he had taken paracetamol, ciprofloxacin, and metronidazole from local pharmacy for tooth ache. Within 3 h of ingestion of the drugs, he developed itching and burning sensation over the acral skin. A few hours later he developed bullae over these sites and erosions on the lips. He had no other drug intake in the last 3 months. His medical records revealed a similar episode 10 months back, which developed a day after taking paracetamol over the same sites. He had received ciprofloxacin for urinary tract infection as an inpatient in 2006 without any adverse reaction. He has tolerated metronidazole on multiple occasions in the past.

On examination the patient was afebrile and stable. Cutaneous examination revealed multiple bullae, a few with prominent hemorrhagic component were noted on the dorsa of hands with erythema near the thenar eminence [Figure 1]. Nikolsky's sign was negative. Erosions and crusting were seen on the lips [Figure 2]. There were no genital lesions. A regular biopsy was done from one of the intact bulla. On histopathological examination, the epidermis revealed foci of basal cell vacuolation, lymphocytic exocytosis, and many necrotic keratinocytes at and above the basal layer. There was also an intraepidermal to subepidermal bulla displaying marked hemorrhage and many neutrophils, a few eosinophils and lymphocytes within its lumen. There was superficial dermal edema and moderate perivascular infiltrates of lymphocytes, histiocytes, neutrophils, and eosinophils. There was no basement membrane thickening or dermal mucin deposits. There were no fungal organisms. Direct immunofluorescence from perilesional skin was negative. Laboratory investigations revealed total white blood cell count 13,200/cu mm with absolute eosinophil count of 160/cu mm. Serum creatinine was normal. Antinuclear antibody was weakly positive. Urine porphyrins and eosinophils were not detected. A diagnosis of bullous FDE to paracetamol was made. The tense bullae were aspirated. The patient was treated with topical steroid-antibacterial preparation for 1 week. On follow-up, resolution of the lesions with surrounding hyperpigmentation was seen. Topical patch test with ciprofloxacin, metronidazole, and paracetamol was negative. Oral provocation testing was refused by the patient. He was counseled to avoid paracetamol in future and to carry a drug alert card.

Figure 1.

(a-c) Multiple bullae, a few with prominent hemorrhagic component, were noted on the dorsa of hands (d) erosions and crusting on the lips

Figure 2.

(a) Intraepidermal to subepidermal hemorrhagic blister with adjacent epidermis showing occasional necrotic keratinocytes (×200). (b) Epidermis with necrotic keratinocytes, basal cell vacuolation, and lichenoid infiltrate seen in the superficial dermis (×40)

Discussion

Paracetamol is a commonly used nonsteroidal anti-inflammatory drug with a reliable safety profile. CADR due to paracetamol is unusual and is generally of fixed type.[10] Bullous variant is still rarer.[10] Systemic manifestations have also been described in patients with FDE, though they are very rare.[4]

In our patient, the temporal correlation with the drug, history of a similar episode and the quick improvement led us to a diagnosis of bullous FDE due to paracetamol. Applying Naranjo's algorithm,[11] a causality score of 8 was obtained and was categorized as probable reaction to paracetamol [Table 1].

Table 1.

Naranjo adverse drug reaction probability scale

In appropriate clinical settings, other differentials to bullous FDE include blistering disorders, bullous lupus erythematosus, linear IgA bullous dermatosis and bullous pemphigoid. FDEs may exhibit anatomical preferences to genitalia, lips, and sacrum.[12] In some patients FDE could be a result of cross-sensitivity if the drugs are closely related, however it does not follow an all or none reaction.[13] A repeat exposure at times may not result in FDE owing to refractoriness, and it could vary from weeks to months.[14] Oral rechallenge is the most reliable technique of identifying the causal agent but can be potentially disastrous. A positive patch test over the previously affected area is a relatively safe method. Lymphocyte transformation tests useful in many types of drug eruptions yield poor results in cases of FDE.[15] Discontinuation of the culprit drug is the main aspect of the management of FDE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

Clinicians should have a high index of suspicion and should be vigilant of the possible adverse reactions to drugs with robust safety profiles. Identification of the offending drug becomes even more challenging in scenarios when the patient is on multiple drug therapy. Drug alert cards could play an important role in preventing recurrences. We report this case to draw attention to a rare side effect of paracetamol, one of the most common over the counter drug.