Nijmegen breakage syndrome and chronic polyarthritis

Srdjan Pasic,Slobodanka Djukic,Maja Kavaric,Tanja Jovanovic,Ivana Lazarevic,Maja Cupic

doi:10.1186/1824-7288-39-59

Srdjan Pasic, Slobodanka Djukic + Show 4 more

Open Access

https://doi.org/10.1186/1824-7288-39-59

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Abstract

We report on pediatric patient with Nijmegen breakage syndrome (NBS), a rare DNA repair disorder characterized by microcephaly, immunodeficiency and predisposition to malignant lymphomas, who developed juvenile idiopathic arthritis (JIA)-like polyarthritis. In patients with primary immunodeficiencies (PID), septic arthritis due to pyogenic bacteria or mycoplasmal arthritis are the most common osteoarticular manifestations. In certain PID, chronic, non-infectious arthritis resembling rheumatoid arthritis may occur. In our patient microbiologic cultures of synovial fluid including Mycoplasma spp. were negative. At first, because of suspected mycoplasmal arthritis we used macrolides and doxycycline combined with hydroxychloroquine but without therapeutic response. However, the use of rituximab led to remission of her polyarthritis lasting for 9 months. Autoimmune features were rarely reported in NBS. An occurrence of JIA-like, chronic polyarthritis in NBS, a DNA repair disorder characterized by decreased tolerance of immunosuppressive drugs such as methotrexate and a high natural risk for lymphomas, makes therapeutic approach even more complex.

Highlights

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive DNA repair disorder characterized by microcephaly, immunodeficiency and cancer [1,2]
We report a juvenile idiopathic arthritis (JIA)-like, chronic polyarthritis in a female patient with NBS
In humoral primary immunodeficiencies (PID), such as X-linked agammaglobulinaemia (XLA) or common variable immunodeficency (CVID), septic arthritis caused with pyogenic bacteria (S.aureus, S. pneumoniae, H.influenzae type b) is the most common osteoarticular manifestation [12]

Summary

Introduction

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive DNA repair disorder characterized by microcephaly, immunodeficiency and cancer [1,2]. During neonatal period intrauterine growth retardation (birth weight, 2700 grams) and microcephaly (head circumference, HC = 31 cm; < p3) were observed Her past medical history revealed that she suffered from recurrent lung infections (otitis media, pneumonia) since infancy. Final diagnosis of NBS was established by mutation analysis of the NBS1 gene that revealed homozygousity for typical 5 base-pair deletion (657del5) She was placed on regular substitution with intravenous immunoglobulin (IVIG) in a dose of 400 milligrams/kg/body weight every 4 weeks. We decided to introduce rituximab in a standard dose regimen (375 mg/m2/month) used in children and adults affected with PID who developed autoimmune diseases [10] She received six infusions of rituximab without major side-effects and continued to receive regular IVIG therapy. Treatment with rituximab led to complete clinical and laboratory remission of her polyarthritis lasting for 9 months (Table 2)

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