title: Granulomatous skin involvement in a patient with an unusual NOD2 mutation.
abstract: Blau syndrome is a rare disorder that is classically characterised by granulomatous arthritis, skin eruptions and uveitis, which occur in the absence of lung involvement. Blau syndrome has been linked to encoding mutations in the NOD-2 gene and is inherited in an autosomal dominant form. The most commonly observed mutations are missense substitutions affecting the arginine residue at position 334. The rare E600A mutation has been described as causing uveitis without skin involvement. Our patient is a 54-year-old man with an unusual heterozygous c.1799A>C(E600A) mutation, who was seen for bilateral lower extremity swelling and pain. On physical examination, he was found to have lower leg oedema with decreased hair growth on the affected area. Biopsy showed non-caseating micro-granulomas consistent with a diagnosis of Blau syndrome. The patient had excellent response to colchicine, but this was stopped because he developed elevated transaminases. Thus, we present an unusual genetic form of a rare condition and we demonstrate skin involvement in a subtype where cutaneous involvement has not hitherto been reported. In addition, the type and presentation of the skin involvement is different from that normally found in classic Blau syndrome. Finally, we report his response to colchicine, although it was ultimately not tolerated by this patient.
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ifedayo O
authors.initials: IO
authors.lastname: Kuye
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Morayo
authors.initials: M
authors.lastname: Adisa
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Rosalynn M
authors.initials: RM
authors.lastname: Nazarian
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Sheila L
authors.initials: SL
authors.lastname: Arvikar
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Gideon P
authors.initials: GP
authors.lastname: Smith
mesh_terms: D001168:Arthritis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D003078:Colchicine / Q000009:adverse effects / Q000627:therapeutic use*; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D012507:Sarcoidosis; D013585:Synovitis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014605:Uveitis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D056660:Hereditary Autoinflammatory Diseases
chemical_list: D006074:Gout Suppressants; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D003078:Colchicine
keywords: Nod2; blau; colchicine; connective tissue disease; sarcoid