What is the most likely cause of a pruritic, limb‑limited spongiotic dermatitis in a 51‑year‑old woman with Crohn’s disease and a carcinoid tumor who is taking ustekinumab (Stelara) and hydroxychloroquine (Plaquenil) and has repeatedly tested negative for celiac disease?

Paradoxical Drug-Induced Spongiotic Dermatitis from Ustekinumab

The most likely cause is paradoxical drug-induced dermatitis from ustekinumab (Stelara), a recognized class effect of biologic therapies in inflammatory bowel disease patients that can manifest as psoriasiform or eczematous eruptions. 1

Pathophysiology and Recognition

Skin lesions occur in approximately 22% of patients with IBD treated with biologics, presenting as either psoriatic (most common) or eczematous patterns 1. While this phenomenon is well-established with anti-TNF agents, paradoxical skin reactions have been documented with ustekinumab despite its mechanism targeting IL-12/23 1. The European Consensus on Extra-Intestinal Manifestations in IBD specifically identifies this as a drug-class effect that can occur across different biologic mechanisms 1.

Key Clinical Features Supporting This Diagnosis:

• Limb-limited distribution is characteristic of paradoxical biologic-induced dermatitis, particularly affecting palms, soles, and extremities 2, 3
• Spongiotic pattern on histology aligns with eczematous-type paradoxical reactions seen with biologics 1, 4
• Pruritic nature is consistent with both psoriasiform and eczematous variants of drug-induced skin reactions 1
• Negative celiac testing effectively excludes dermatitis herpetiformis, which would be the primary celiac-associated dermatologic manifestation 1

Documented Cases with Ustekinumab

Case reports have specifically documented paradoxical pustular and psoriasiform eruptions with ustekinumab in Crohn's disease patients 2, 3. One case described subcorneal pustular dermatosis appearing 5 weeks after UST induction, recurring with maintenance dosing 2. Another documented paradoxical palmoplantar pustular psoriasis appearing 3 weeks after UST initiation 3. These cases establish that ustekinumab can induce paradoxical skin reactions despite its different mechanism from anti-TNF agents.

Hydroxychloroquine Consideration

While hydroxychloroquine (Plaquenil) can cause dermatologic reactions, these typically manifest as hyperpigmentation, photosensitivity, or exfoliative dermatitis rather than spongiotic dermatitis 5. The FDA label for Plaquenil emphasizes dermatologic reactions requiring caution but does not specifically describe spongiotic patterns 5.

Management Algorithm

Initial Approach:

• Dermatology referral is mandatory for definitive diagnosis and biopsy confirmation 1
• Continue ustekinumab initially while implementing topical therapy, as most cases (approximately 50%) respond without drug discontinuation 1

First-Line Treatment:

• Topical corticosteroids (medium-to-high potency) 1
• Topical emollients and keratolytics (salicylic acid, urea) 1
• Oral antihistamines for pruritus management 1

If Inadequate Response:

• Consider vitamin D analogues or narrow-band UVB phototherapy 1
• Topical calcineurin inhibitors (tacrolimus, pimecrolimus) may be effective 1

Severe or Refractory Cases:

• Systemic corticosteroids (prednisone 0.5-1 mg/kg) may be necessary 1
• Drug discontinuation should be considered only if topical measures fail and skin disease significantly impacts quality of life 1
• Switching to vedolizumab may be considered, as it has gut-specific immunosuppression with potentially lower dermatologic toxicity 1

Critical Pitfalls to Avoid

Do not automatically discontinue ustekinumab upon rash appearance—the European Consensus emphasizes that most cases are controlled with topical treatment while maintaining the biologic 1. This is crucial given that ustekinumab demonstrates 67.7% clinical remission rates at 6 months in Crohn's disease 6, and discontinuation risks disease flare.

Switching between biologics may not resolve the issue, as this appears to be a class effect across different mechanisms 1. One case report showed recurrence even after switching from ustekinumab to golimumab 3.

Do not assume this represents treatment failure—paradoxical reactions are distinct from loss of therapeutic efficacy and do not necessarily indicate the need for escalation of IBD therapy 1.

Carcinoid Tumor Consideration

The patient's carcinoid tumor is unlikely to be causative, as carcinoid syndrome typically produces flushing rather than persistent spongiotic dermatitis 4. However, eosinophilia associated with carcinoid syndrome could theoretically contribute to inflammatory skin manifestations and should be monitored 4.