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Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome
Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)—a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585138/ https://www.ncbi.nlm.nih.gov/pubmed/37868966 http://dx.doi.org/10.3389/fimmu.2023.1279329 |
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author | Jensen, Mary Ellen Harrell, Katelin McBride, Jeffrey D. |
author_facet | Jensen, Mary Ellen Harrell, Katelin McBride, Jeffrey D. |
author_sort | Jensen, Mary Ellen |
collection | PubMed |
description | Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)—a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component (“naked granulomas”), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously. |
format | Online Article Text |
id | pubmed-10585138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105851382023-10-20 Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome Jensen, Mary Ellen Harrell, Katelin McBride, Jeffrey D. Front Immunol Immunology Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)—a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component (“naked granulomas”), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously. Frontiers Media S.A. 2023-10-05 /pmc/articles/PMC10585138/ /pubmed/37868966 http://dx.doi.org/10.3389/fimmu.2023.1279329 Text en Copyright © 2023 Jensen, Harrell and McBride https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Jensen, Mary Ellen Harrell, Katelin McBride, Jeffrey D. Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome |
title | Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome |
title_full | Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome |
title_fullStr | Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome |
title_full_unstemmed | Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome |
title_short | Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome |
title_sort | case report: methotrexate and hydroxychloroquine in combination for the treatment of nod2-mutation-associated blau syndrome |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585138/ https://www.ncbi.nlm.nih.gov/pubmed/37868966 http://dx.doi.org/10.3389/fimmu.2023.1279329 |
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