# Upadacitinib-Induced Remission in Multicentric Reticulohistiocytosis: Expanding the Therapeutic Role of JAK Inhibition

## TL;DR

A 60-year-old woman with a rare disease called multicentric reticulohistiocytosis achieved full remission using a JAK1 inhibitor called upadacitinib, offering new hope for treating this condition.

## Contribution

This case demonstrates the effectiveness of upadacitinib in treating refractory multicentric reticulohistiocytosis with multisystem involvement.

## Key findings

- Upadacitinib induced rapid and complete remission of cutaneous and articular disease.
- Pulmonary involvement showed improvement with upadacitinib treatment.
- Secondary weight gain and diabetes were managed with tirzepatide.

## Abstract

Multicentric reticulohistiocytosis (MRH) is a rare systemic histiocytic disorder of uncertain etiology characterized by papulonodular cutaneous lesions and potentially destructive polyarthritis, with variable multisystem involvement. Owing to its low prevalence, evidence for optimal management remains limited, and treatment responses are heterogeneous. Emerging reports suggest that Janus kinase (JAK) inhibition may provide benefit in refractory disease. We report a 60-year-old woman with MRH presenting with papulonodular skin lesions, symmetric polyarthritis, constitutional symptoms, and interstitial lung disease (nonspecific interstitial pneumonia pattern) in the context of co-existing primary biliary cholangitis and no evidence of malignancy. Prior therapies (glucocorticoids, methotrexate, leflunomide) achieved suboptimal control. Upadacitinib, a selective JAK1 inhibitor, induced rapid and complete remission of cutaneous and articular disease with improvement of pulmonary involvement. Secondary weight gain and incident diabetes were managed with tirzepatide. This case adds to the limited literature supporting JAK inhibition as a targeted option for refractory MRH, including multisystem disease with pulmonary involvement. Systematic evaluation of efficacy, durability, and safety is warranted.