Multicentric Reticulohistiocytosis Exhibiting Positive HLA-B*07 and HLA-B*08: A Case Report

Elena Rezuș,Danisia Haba,Romică Sebastian Cozma,Anca Cardoneanu,Mihai Danciu,Ciprian Rezuș,Maria Alexandra Burlui

doi:10.3390/medicina56090456

Abstract

Multicentric reticulohistiocytosis (MRH) is a rare cause of destructive inflammatory arthritis involving both small, as well as larger joints. We report the case of a 40-year-old Caucasian female with a family history of neoplasia who was referred to our service witha two-month history of inflammatory joint pain. On examination, the patient had inflammatory arthritis, mainly involving the peripheral joints, sacroiliac joint pain, and numerous papulonodular mucocutaneous lesions, including periungual “coral beads”. Imaging tests revealed erosive arthritis with synovitis and tenosynovitis, sacroiliac joint changes, as well as papulonodular mucosal lesions in the nasal vestibule, the oropharyngeal mucosa, and supraglottic larynx. She tested positive for HLA-B*07 (Human Leukocyte Antigen B*07) and HLA-B*08, ANA (antinuclear antibodies), RF (rheumatoid factor), anti-Ro52, anti-SSA/Ro, and anti-SSB/La antibodies. The skin biopsy was suggestive of MRH, showing a histiocyte infiltrate and frequent giant multinucleated cells. The patient exhibited favorable outcomes under Methotrexate, then Leflunomide. However, she displayed worsening clinical symptoms while under Azathioprine. To our knowledge, this is the first case of MRH to exhibit positive HLA-B*07 together with HLA-B*08. The rarity of MRH, its unknown etiology and polymorphic clinical presentation, as well as its potential neoplastic/paraneoplastic, and autoimmune nature demand extensive investigation.

Highlights

Multicentric reticulohistiocytosis (MRH) is a multisystem granulomatous non-Langerhans cell histiocytosis and a very rare cause of destructive inflammatory arthritis [1].MRH has been classified as a C-Group histiocytosis, Medicina 2020, 56, 456; doi:10.3390/medicina56090456 www.mdpi.com/journal/medicinaMedicina 2020, 56, 456 in the subgroup with notable systemic involvement [2]
The infiltrate of CD163+, CD68R+, CD1a− large mono- to multinucleated cells with ground-glass cytoplasmin the biopsy specimens of the affected tissues depicts the histological mark of MRH [1,3]
It has been hypothesized that patients with MRH may harbor mutations of the oncogene BRAF

Summary

Introduction

Multicentric reticulohistiocytosis (MRH) is a multisystem granulomatous non-Langerhans cell histiocytosis (non-LCH) and a very rare cause of destructive (erosive) inflammatory arthritis [1]. MRH has been classified as a C-Group histiocytosis (non-LCH involving both skin and mucosae), Medicina 2020, 56, 456; doi:10.3390/medicina56090456 www.mdpi.com/journal/medicina. It has been hypothesized that patients with MRH may harbor mutations of the oncogene BRAF (B-Raf Proto-Oncogene Serine-Threonine Kinase), as well as MAP2K1 Kinase Kinase 1), which are both involved in the RAS-MAPK (Ras/Mitogen-Activated Protein Kinase) signaling pathway and could be relevant as therapeutic targets [4,5]. The authors proposed that MRH be classified as a neoplastic condition, given that its pathomechanism may involve the activation of the RAS-MAPK pathway [6]. We have obtained approval from the Ethics Committee for the present work (10371/29.04.2020)

Case Report

Paraclinical

Cone-beam

Discussion

Conclusions