Abstract
To the Editor:
Systemic contact dermatitis (SCD) is a type IV delayed hypersensitivity reaction that occurs when a previously sensitized individual is re-exposed to a contact allergen through systemic routes, such as oral, parenteral, or other pathways. 1 Unlike classical contact dermatitis, which remains confined to the site of exposure, SCD typically presents as generalized or distant eczematous eruptions. While SCD is well documented with metals and certain medications, corticosteroid-induced SCD remains underrecognized, despite its paradoxical nature. Among corticosteroids, oral prednisolone represents an exceptionally rare trigger. This phenomenon, where an anti-inflammatory agent provokes an inflammatory reaction, poses significant diagnostic and therapeutic challenges. We report a case of prednisolone-induced SCD, emphasizing the critical role of pharmaceutical excipients in mediating delayed-type hypersensitivity reactions.
A 74-year-old man with a 3-year history of dyshidrotic eczema of the hands, managed intermittently with topical corticosteroids, was admitted for organizing pneumonia complicating chronic obstructive pulmonary disease. Treatment was initiated with effervescent prednisolone (20 mg/day). Within 72 hours of the first dose, he developed pruritic erythematous and vesicular eruptions on the abdomen, arms, thighs, and buttocks (Fig. 1). The initial flare resolved spontaneously within 24 hours; however, a more severe recurrence occurred just 3 hours after the second dose. The eruption cleared completely after withdrawal of prednisolone, strongly suggesting SCD induced by this treatment, as no other potential triggers were identified. Comprehensive patch testing revealed a strong positive reaction to Balsam of Peru (++/++/++) at 48-hour, 72-hour, and 7-day readings, whereas prednisolone itself produced only equivocal responses (Fig. 2). These results were consistent with the excipient profile of the effervescent formulation, which contained Balsam of Peru derivatives such as benzoates and various flavoring agents. Patch tests with the corticosteroid series were negative, excluding true corticosteroid allergy. Clinical relevance was further demonstrated by the patient’s subsequent tolerance of prednisone, a corticosteroid lacking these excipients, with no recurrence of symptoms. Sustained remission was achieved after strict avoidance of prednisolone, related corticosteroids containing similar excipients, and products with Balsam of Peru derivatives.
The patch test showed a positive reaction to Balsam of Peru at H72.
Our case illustrates a rare but clinically significant example of SCD induced by oral prednisolone, most likely mediated by hypersensitivity to excipients rather than the corticosteroid itself. It further highlights the essential role of pharmaceutical excipients in eliciting SCD, particularly when the active compound yields equivocal or negative patch test results. 2 The patient’s strong reactivity to Balsam of Peru, an excipient in the effervescent prednisolone formulation, demonstrates how inactive ingredients can serve as primary sensitizers in delayed-type hypersensitivity reactions. This observation underscores the importance of assessing both active and inactive components in drug-related hypersensitivity. 3
The paradoxical nature of corticosteroid-induced SCD presents unique diagnostic challenges, since the anti-inflammatory properties of these agents may initially mask hypersensitivity manifestations. 4 Nonetheless, the characteristic clinical presentation, rapid onset (within 48 hours), dose-dependent recurrence, and distinctive vesicular lesions in non-contact areas provide valuable diagnostic clues. The patient’s history of chronic dyshidrotic eczema treated with topical corticosteroids likely served as the initial sensitizing factor, consistent with reports that cutaneous exposure may predispose to systemic reactions upon subsequent oral or parenteral administration. 5
From a mechanistic standpoint, this case challenges conventional assumptions regarding cross-reactivity patterns in drug hypersensitivity. The dissociation between patch test results and clinical reactivity demonstrates that corticosteroid hypersensitivity does not always conform to predicted structural classifications. 6
For optimal management of similar cases, clinicians should ensure strict avoidance of identified triggers, carefully select alternative corticosteroids with distinct excipient profiles, and consider gradual reintroduction under medical supervision when corticosteroid therapy is unavoidable. This case serves as a crucial reminder that unexplained eczematous eruptions during systemic corticosteroid therapy should raise suspicion for SCD. A thorough evaluation of pharmaceutical excipients remains fundamental to achieving accurate diagnosis and effective management of these complex drug reactions.