Oral upadacitinib 15 mg once daily produced near-complete resolution of refractory acquired reactive perforating collagenosis (ARPC) within 8 weeks in a 72-year-old man with atopic dermatitis (AD), type 2 diabetes and stage 4 chronic kidney disease (CKD) — after a single 600 mg dupilumab dose triggered paradoxical worsening within 24 hours.

The case, published in Frontiers in Medicine on October 7, 2026, by Wang and colleagues, adds real-world evidence for selective JAK1 inhibition in a perforating dermatosis phenotype that pivotal AD trials have largely excluded: patients with severe renal impairment. Remission held at one-year follow-up, three months after upadacitinib was stopped at nine months.

What did the case show numerically?

The effect sizes were unambiguous:

• Pruritus (PP-NRS) fell from 9 to 2 after 3 weeks of upadacitinib.
• SCORAD dropped from 48.8 at baseline to 29 at week 3 and to 8 at week 8.
• Total serum IgE normalized by week 8 (from 654.15 IU/mL at initiation).
• At 9 months, all papules and nodules had resolved and pruritus was nearly eliminated.
• Creatinine clearance remained stable throughout treatment at 15.5–23 mL/min, with no adverse effects observed.

The patient presented with a 5-year history of generalized erythema, papules and nodules with severe pruritus, and a baseline laboratory profile that constrained every conventional option: HbA1c 11.6%, creatinine 298.43 μmol/L, creatinine clearance 24.3 mL/min, eosinophilia of 1.90 × 10⁹/L, elevated IL-4 (8.54 pg/mL) and IL-6 (19.13 pg/mL), and total IgE of 581.61 IU/mL. AD was diagnosed by Chinese Zhang's criteria. Histopathology confirmed ARPC, showing transepidermal elimination of collagen fibers through the ulcer bed, with Verhoeff-van Gieson staining demonstrating collagen traversing the ulceration.

Why did dupilumab fail?

Within 24 hours of a single 600 mg loading dose, the patient developed extensive edematous erythema and bright-red papules on the face, neck, trunk and upper extremities with severe pruritus. Clinicians suspected a paradoxical reaction, treated with intramuscular dexamethasone 5 mg daily for five days, then oral methylprednisolone, and permanently discontinued dupilumab — a decision reinforced by flow cytometry showing relative immunosuppression (CD4/CD8 ratio 4.02, absolute lymphocytes 700/μL).

The authors argue the failure was mechanistic, not idiosyncratic. The combined metabolic burden of poorly controlled diabetes and stage 4 CKD activated non-Th2 pathways — JAK-dependent IL-31, Th17-related cytokines, and TGF-β-mediated fibrotic remodeling — leaving isolated IL-4Rα blockade insufficient. Advanced glycation end products and uremic toxins drove dermal microangiopathy, collagen degeneration and neuronal sensitization, sustaining the itch-scratch cycle.

Two years of interim therapy — systemic corticosteroids, antihistamines, thalidomide, topical halometasone and antibiotics — produced only limited benefit with relapse on every steroid taper.

How does upadacitinib fit in advanced CKD?

Pre-treatment screening (hepatic function, lipids, CRP, repeat IGRA, chest CT) showed no contraindications. Notably, the patient had previously failed tofacitinib, a non-selective JAK1/3 inhibitor — which the authors read as evidence that JAK1 selectivity is a critical determinant of efficacy in refractory ARPC.

Pharmacokinetic data cited in the report show the AUCinf for upadacitinib 15 mg once daily rises 18%, 33% and 44% in mild, moderate and severe renal impairment respectively, and dose adjustment is not recommended. The authors also cite the head-to-head trial (Blauvelt et al., JAMA Dermatology, 2021) in which upadacitinib showed greater efficacy than dupilumab at week 16 in moderate-to-severe AD.

The authors position their case against prior JAK-inhibitor reports in ARPC — upadacitinib, baricitinib and tofacitinib — most of which involved patients without severe renal impairment. Sustained remission after discontinuation also contrasts with published relapse following baricitinib withdrawal, and they flag the counterexample of ARPC arising secondary to upadacitinib in severe eczema as a reminder that the same agent can produce divergent outcomes depending on comorbidities and immune context.

The evidence remains a single case. The authors call for prospective studies to define optimal treatment duration and discontinuation strategies for upadacitinib in refractory ARPC.