A predominantly left-sided skin reaction to pristinamycin in a patient with right hemiplegia

Introduction

Unilateral skin reactions are rare in patients with neurologic impairments caused by vascular or metastatic disease. The pathophysiology of these unilateral reactions has not been characterized, although recent research in neurophysiology provides a few clues.

Case report

Mr A (a 49-year-old man with right hemiplegia for the previous 18 months as a result of an ischemic stroke) was treated with pristinamycin (1 g, 3 times a day) for erysipelas of the right leg.

The patient had coronary heart disease and a history of alcohol and tobacco consumption. There had been no recent changes in his medications. He was treated for 2 years with amlodipine, baclofen, bisoprolol, cetirizine, fluoxetine, lysine acetylsalicylate, levetiracetam, pregabalin, rabeprazole, and atorvastatin. Seven days after the initiation of antibiotic treatment, he presented with left-sided maculopapular exanthema (MPE) on the trunk and the lower and upper limbs. The skin eruption was less widespread on the right upper and lower limbs (Figs 1 and 2). The patient did not have fever, mucosal erosions, skin blisters, adenopathy, digestive symptoms, or any severe systemic signs suggestive of a viral infection. The Naranjo score was 4, which means that an adverse drug reaction caused by pristinamycin was possible. Laboratory tests found hypereosinophilia (0.6 g/L) but no other abnormalities. Histologic analysis of the skin biopsy found an eczemalike pattern with a few necrotic keratinocytes and eosinophilic, perivascular, and dermal infiltration (Fig 3). We diagnosed a predominantly left-sided, MPE-type adverse reaction of the skin due to pristinamycin. The eruption resolved within 10 days (with no need for treatment other than pristinamycin withdrawal) and did not recur.

Fig 1.

Maculopapular exanthema, left-sided.

Fig 2.

Maculopapular exanthema, left-sided.

Fig 3.

Eczemalike pattern with a few necrotic keratinocytes and eosinophilic, perivascular, dermal infiltration. (Hematoxylin-eosin-safran stain.)

Discussion

Cutaneous side effects of pristinamycin (an antibiotic related to the macrolides) are rare. The most frequently reported adverse events of this kind are delayed-type, MPE-like reactions. There are also some reports of type 1 hypersensitivity (urticaria and angioedema), Steven Johnson syndrome, Lyell syndrome, acute generalized pustulosis, drug reactions with eosinophilia and systemic symptoms, and even a pityriasis rosea–like eruption. In view of the absence of other likely etiologies (and especially viral causes), the chronology of the eruption, and the fact that MPE-like reactions are the most frequent delayed-type hypersensitivity (DTH) skin reaction to antibiotics in general and to pristinamycin in particular, we considered that the MPE was an adverse reaction to the antibiotic. We would have preferred to perform skin tests to confirm this hypothesis, but, unfortunately, the patient was lost to follow-up soon after this episode. Bilateral skin tests might have reproduced the predominantly left-sided reactivity, although this type of exposure to the allergen might have triggered hyperresponsiveness of the skin (sometimes referred to angry back or excited skin syndrome) or an even more serious systemic reaction.

We found 5 other literature reports of unilateral adverse skin reactions: 2 cases involved the targeted therapies, sorafenib and cetuximab, and the 3 others involved the antimitotics, capecitabine and docetaxel (Table I). Several pathophysiologic hypotheses may be considered. It is thought that hand-foot syndrome (HFS) may result from mechanical stress. Hence, hemiplegia might protect the affected side from this type of syndrome.¹ Given that many stroke patients have atherosclerosis, poor vascular flow might result in a lower concentration of drug metabolites (and thus a lower risk of HFS development) on the paretic side.² Abnormal innervation and lower levels of microtrauma on the paralyzed side might slow nail growth and thus reduce the risk of onycholysis. Lastly, lymphatic stasis might account for folliculitis on the paralyzed side because of the persistence of cetuximab binding to the epidermal growth factor receptor.⁵ The latter hypothesis was already been suggested in a report on unilateral pemphigoid in a hemiplegic patient.⁶ However, none of the aforementioned side effects were immune reactions like MPE. To the best of our knowledge, a predominantly unilateral, MPE-like skin reaction (ie, one with an immunoallergic mechanism) has not been described previously. The etiology of unilateral MPE has not been characterized, although several hypotheses can be considered. As mentioned above, lower levels of microtrauma and lymphatic stasis on the paralyzed side might protect the body by slowing down the flow of inflammatory mediators.

Table I.

Unilateral adverse reactions: 5 case reports from the literature

Study	Unilateral adverse reaction/body side	Neurologic disorder	Drug
Almeida da Cruz et al1	Right HFS	Left hemiplegia	Capecitabine
Disel et al2	Left HFS	Right hemiplegia	Capecitabine
Truchuelo et al3	Onycholysis of the right hand	Left hemiplegia	Docetaxel
Chanal et al4	Right HFS	Hemiplegia of the left arm	Sorafenib
Kerob et al5	Right facial folliculitis	Right facial palsy	Cetuximab

However, we propose a new hypothesis: immune impairment on the paralyzed side (probably related to T lymphocytes) may reduce the incidence or severity of exanthema. The relationships between the immune system and the central nervous system have been studied since the 1980s. Lévine et al⁷ and then Tarkowski et al⁸ reported that T cell immunity was asymmetric in hemiplegic patients. On the basis of the reactions to intradermal injections of tuberculin, these researchers found that patients with brain lesions caused by stroke displayed lateralized, DTH reactions.

The lateralization of DTH responses changed over time and was related to the severity, site, and the stroke phase (acute vs chronic).⁹ Patients in the early phase of a minor stroke displayed a less-intense DTH response on the paretic side than on the nonparetic side, whereas patients with major stroke displayed a larger DTH response on the paretic side than on the nonparetic side.⁹ The lateralization may be reversed in the chronic phase, regardless of the stroke's severity.¹⁰

We observed a rare case of a unilateral adverse skin reaction on the valid body side of a patient with stroke-induced hemiplegia. This case illustrates that poststroke immune impairments may occur on the paralyzed side.