We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. [ncbi.nlm.nih.gov]

• Retinal Lesion

  This report illustrates the presence of a remarkable distribution of perivascular, presumably granulomatous, retinal lesions in the middle retina. [ncbi.nlm.nih.gov]

• Eczema

  “When we took her in to see her primary care physician, he said it was eczema.” However, Makenna’s parents were not convinced by the doctor’s hasty diagnosis, so they consulted a dermatologist to get a biopsy. [childrensinn.org]

  […] have these symptoms is not available through HPO Abnormal cranial nerve morphology 0001291 Abnormality of the ear 0000598 Arthritis Joint inflammation 0001369 Autosomal dominant inheritance 0000006 Band keratopathy 0000585 Cystoid macular edema 0011505 Eczema [rarediseases.info.nih.gov]

  STAT5b deficiency Modestly decreased Normal Normal Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstital pneumonitis AR Defects of STAT5B gene, impaired development and function of γδT cells, Treg and NK cells, impaired [ncbi.nlm.nih.gov]

  Other times, a common skin condition such as psoriasis (pictured) or eczema might affect a person's appearance. But some folks have health conditions that result in permanently atypical skin. [cbsnews.com]

• Arthralgia

  Gender (female:male) 13:9 Mean age at diagnosis 40.1 years (range 17-72) Mean disease duration 4.7 years (range 1-13) Ethnicity (white) 22/22 (100%) Familial 3/22 (13.6%) Weight loss 13/22 (59.1%) Fever 13/22 (59.1%) Skin disease 19/22 (86.4%) Arthritis/arthralgia [clevelandclinicmeded.com]

  Joint pains There are often joint pains (arthralgias or arthritides), but generally NO tissue and cartilage changes can be seen on X rays. [autoinflammatory.org]

  Affiliated tissues include eye, skin and kidney, and related phenotypes are arthralgia and joint swelling Disease Ontology : 12 A syndrome characterized by familial granulomatous arthritis, uveitis and skin granulomas. [malacards.org]

  Corticosteroid treatment should be resumed for recurrence of symptoms and signs, including dyspnea, arthralgia, fever, hepatic insufficiency, cardiac arrhythmia, CNS involvement, hypercalcemia, ocular disease uncontrolled by local drugs, and disfiguring [merckmanuals.com]

• Neurologic Manifestation

  Ömer Faruk Aydin and Banu Anlar, Neurological Manifestations of Primary Immunodeficiency Diseases, Clinical Pediatrics, 10.1177/0009922817737083, (000992281773708), (2017). Leonardo A. [doi.org]

  manifestations have been reported in familial and sporadic cases, especially in the form of cranial neuropathies and transient facial palsy. 31 Recently, in a patient carrying a G481D mutation, in addition to transient facial palsy, ischaemic stroke [rmdopen.bmj.com]

During the diagnostic workup, he had worsening of ocular complaints, retinal exam showed panuveitis with multifocal choroiditis. [hindawi.com]

• Fibrinoid Necrosis

  RESULTS: Biopsy specimens from patients with BS typically showed polycyclic granulomas with large lymphocytic coronas, extensive emperipolesis of lymphocytes within multinucleated giant cells (MGCs), MGC death, and fibrinoid necrosis and fibrosis. [ncbi.nlm.nih.gov]

• Lymphocytic Infiltrate

  We report a 3.5-year-old Japanese boy who developed lichenoid papules and erythema with noncaseating epithelioid cell granulomas with a scant lymphocytic infiltrate histologically on his limbs at the age of 8 months. [ncbi.nlm.nih.gov]

• HLA-DR4

  Although HLA haplotypes do not appear to segregate with affected subjects, HLA-DR2 and HLA-DR4 subtypes may play a permissive role in phenotype expression. [ncbi.nlm.nih.gov]

• HLA-DR2

  Although HLA haplotypes do not appear to segregate with affected subjects, HLA-DR2 and HLA-DR4 subtypes may play a permissive role in phenotype expression. [ncbi.nlm.nih.gov]

Ocular disease remained persistently active despite treatment with multiple different immunosuppressants; therefore, canakinumab treatment was started. [ncbi.nlm.nih.gov]

At follow up at 20 years of age (after 2-5 years of infliximab treatment) the twins had an almost normal physical appearance and a normal psychomotoric development, indicating a favourable short-term prognosis of the disease. [ncbi.nlm.nih.gov]

Prognosis BS is a chronic and progressive disease with a variable and often unpredictable spectrum of severity. In cases with expanded manifestations, life expectancy may be reduced. Uveitis has a poor prognosis. [orpha.net]

However, the activity of the disease may fluctuate over time. 2.10 What is the long-term prognosis (predicted outcome and course) of the disease? The available data concerning the prognosis in the long-term is limited. [printo.it]

Early treatment with a biologic agent may improve the prognosis. sarcoidosis inflammation early rheumatoid arthritis Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will [ard.bmj.com]

NOD2/CARD15 genotyping before transplantation may contribute to prognosis and influence clinical management. [ PMID 18756601 ] No association was found for NOD2/CARD15 SNPs (R702W, G908R) in Chinese patients with inflammatory bowel disease. [snpedia.com]

The aim of this study was to assess the efficacy of thalidomide in patients with severe EOS, based on etiology supporting an initial role of NF-kappaB in activation of this disease. [ncbi.nlm.nih.gov]

These findings indicate that the majority of EOS and BS cases share the common genetic etiology of CARD15 mutations that cause constitutive NF-κB activation. Submitted August 2, 2004. Accepted September 27, 2004. [bloodjournal.org]

Etiology BS is due to an inherited or de novo mutation in the NOD2 gene (16q12), responsible for alterations in the innate immune response, inflammation and cell death. [orpha.net]

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome. Blood. 2005 Feb 1;105(3):1195-7. Epub 2004 Sep 30. [ghr.nlm.nih.gov]

Summary Epidemiology Exact prevalence is unknown. [orpha.net]

A review of epidemiology, pathophysiology, and therapeutic implications, Inflammatory Bowel Diseases, 10, 6, (848-859), (2006). [doi.org]

Epidemiology and Demographics The prevalence of Blau syndrome has been reported less than 0.1 per 100,000 individuals worldwide.[5] Blau syndrome commonly affects individuals younger than 4 years of age. [wikidoc.org]

Epidemiology: Blau syndrome is a very rare disease. [eyewiki.aao.org]

Previous epidemiologic studies have shown that mutations in the NOD2/CARD15 gene are extremely rare outside the white population. 8 Second, our observed rates of GVHD were also lower than earlier studies, which may reflect our exclusion of any donor-recipient [bloodjournal.org]

Signaling protein and cytokine expression were examined, and the results of these experiments challenge current theories of constitutive NOD2 activation in the pathophysiology of Blau syndrome. [ncbi.nlm.nih.gov]

Even though specific treatment based on pathophysiologic mechanism has not been explored yet, early diagnosis will prevent the progression to severe impairment, which can severely affect patients' lives. [jstage.jst.go.jp]

A review of epidemiology, pathophysiology, and therapeutic implications, Inflammatory Bowel Diseases, 10, 6, (848-859), (2006). [doi.org]

Etiology Pathophysiology The NOD2 protein is part of the NOD family of proteins. [dermatologyadvisor.com]

There is no established therapy for the management of BS and EOS, and the main treatment aim is to prevent ocular manifestations entailing the risk of potential blindness and to avoid joint deformities. [ncbi.nlm.nih.gov]

Even though specific treatment based on pathophysiologic mechanism has not been explored yet, early diagnosis will prevent the progression to severe impairment, which can severely affect patients' lives. [jstage.jst.go.jp]

This gene produces a protein which is part of the body’s immune system, helping to prevent foreign invaders from damaging the body. When the NOD2 gene is affected, that response is overactive, causing the severe inflammation, pain and skin rash. [skinsite.com]

Saito added the study implies that preventing IFN-γ activation could benefit patients. "Blocking IFN-γ signaling could be a potential treatment for managing chronic inflammation." [cira.kyoto-u.ac.jp]

Mahbub, Hidekazu Takahashi, Ryosuke Hase, Yasutaka Ishimaru, Hiroshi Sunagawa, Rie Watanabe, Yoshinobu Eishi & Tsuyoshi Tanabe Environmental Health and Preventive Medicine (2017) [nature.com]