Syringotropic hypersensitivity reaction associated with infliximab and leflunomide combination therapy in a child with psoriatic arthritis

Abstract

A 17-year-old boy with refractory psoriatic arthritis and alpha-1 antitrypsin deficiency who developed a syringotropic hypersensitivity reaction after 9 months of therapy with infliximab and leflunomide is described. Clinically, our patient showed a vasculitic-like skin rash involving both palms and soles, and histopathological examination revealed a syringotropic lymphocytic infiltrate directed toward the intra-epidermal portion of the eccrine ducts. These features have not been previously associated with infliximab or leflunomide therapy and represent a unique cutaneous hypersensitivity reaction that does not fit any known description of an immune-mediated hypersensitivity reaction.

Broad range of adverse cutaneous eruptions in patients on TNF‐alpha antagonists

“…15 Leukocytoclastic vasculitis was reported in 35 patients undergoing infliximab or etanercept therapy among the US Food and Drug Administration Adverse Events Reporting System. 66 Most cases (62.8%) improved or resolved upon cessation of anti-TNF agent. 72 A favorable outcome of anti-TNF therapyinduced vasculitis was also showed by a case series of three rheumatoid arthritis patients; one of whom improved upon cessation of therapy, and the remaining two with clinical improvement following oral corticosteroid treatment.…”

“…More recently, neutrophilic eccrine hidradenitis has been reported as an infrequent side effect of imatinib mesylate, a tyrosine kinase inhibitor 65 . A case of infliximab and leflunomide combination therapy‐associated syringotropic hypersensitivity reaction has been described in which a mononuclear cell infiltrate comprised predominantly of CD4+ T helper lymphocytes affecting the acrosyringium and papillary dermal eccrine ducts was showed 66 …”

“…More recently, 113 cases of vasculitis (most commonly leukocytoclastic vasculitis) among 233 total cases of autoimmune diseases induced by TNF‐targeted therapies were reported, 25% with extracutaneous manifestations 15 . Leukocytoclastic vasculitis was reported in 35 patients undergoing infliximab or etanercept therapy among the US Food and Drug Administration Adverse Events Reporting System 66 . Most cases (62.8%) improved or resolved upon cessation of anti‐TNF agent 72 .…”

Leflunomide in dermatology

“…Other dermatologic diseases precipitated by leflunomide include a mucocutaneous lichen planuselike eruption, 40 a photodistributed lichenoid drug reaction, 41 Reiter syndrome, 42 leukocytoclastic vasculitis, 43,44 leg ulcers, 45 alopecia areata, 46 and a syringotropic hypersensitivity reaction. 47 Two patients with psoriatic arthritis also developed truncal ulcerations that improved after drug washout with cholestyramine. 48,49 The only cutaneous infection reported in a patient treated with leflunomide was a subcutaneous infection with Stenotrophomonas maltophilia of the lower leg that resolved with oral ciprofloxacin administration.…”

Update in drug allergy: novel drugs with novel reaction patterns

“…A series of unique reports has been made: first, a syringotropic hypersensitivity reaction (syringotropic mononuclear cell infiltrate directed mainly toward distal eccrine ducts in the papillary dermis and within the epidermis) after therapy with infliximab and leflunomide [27]. Second, an overlap syndrome in a Chinese lady with systemic lupus erythematosus who presented with features of acute generalized exanthematous pustulosis (AGEP), but evolved to AGEP-toxic epidermal necrolysis overlap as an adverse reaction to hydroxychloroquine [28].…”