Rare diseases: What rheumatologists need to know?

do Nascimento, Renan Rodrigues Neves Ribeiro; Piotto, Daniela Gerent Petry; Freire, Eutilia Andrade Medeiros; de Souza Neves, Fabricio; Sztajnbok, Flavio Roberto; Bica, Blanca Elena Rios Gomes; Pinheiro, Frederico Augusto Gurgel; Kozu, Katia Tomie; Pereira, Ivanio Alves; Azevedo, Valderilio Feijo; Cordeiro, Rafael Alves; Giardini, Henrique Ayres Mayrink; Franco, Marco Túlio Muniz; de Fátima Fernandes Carvalho, Margarida; Rosa-Neto, Nilton Salles; Perazzio, Sandro Félix

doi:10.1186/s42358-024-00407-6

Advances in Rheumatology

Table 2 Autoinflammatory diseases

From: Rare diseases: What rheumatologists need to know?

Disease	Gene	Inheritance	Clinical features	Laboratory tests	Treatment
FMF and PAAND	MEFV	AR and AD	Fever, serositis, pleural effusion peritonitis, arthritis, erysipelas-like erythema (rash)	Increased IM during disease flares. In severe cases, renal biopsy may show amyloid deposits; Molecular analysis^#	Colch, CS, IL-1i, TNFi, IL-6i
CAPS (NOMID/CINCA, MWS, FCAS)	NLRP3	AD	Fever, urticarial rash, aseptic meningitis, hearing loss, conjunctivitis, optical nerve atrophy, abnormal endochondral bone growth	Increased IM during disease flares. In severe cases, renal biopsy may show amyloid deposits; Molecular analysis^#	CS, IL-1i
MKD	MVK	AR	Fever, abdominal pain, lymphadenopathy, rash, oral and genital ulcers, hepatosplenomegaly	Increased IM and IgD serum levels during disease flares. Elevated levels of urinary mevalonic acid; Molecular analysis^#	CS, IL-1i, TNFi, I IL-6i, Colch
TRAPS	TNFRSF1A	AD	Fever, abdominal pain, migratory rash with fasciitis, periorbital rash, serositis, conjunctivitis	Increased IM during disease flares; Molecular analysis^#	CS, TNFi, IL-1i, IL-6i, Colch
PAPA, hyperzincemia and hyper-calprotecnemia syndrome	PSTPIP1	AD (variable penetrance)	Destructive arthritis, neutrophilic dermatoses (especially pyoderma gangrenosum), inflammatory skinrash, myositis	Increased IM during disease flares; Molecular analysis^#	CS, TNFi, IL-1i, IL-6i
VEXAS syndrome	UBA1	Somatic mutation	Fever, rash (neutrophilic dermatoses), interstitial lung disease, vasculitis, arthralgia, arthritis, polychondritis, thrombosis, serositis, myocarditis, hepatosplenomegaly	Increased IM during disease flares. Macrocytic anemia, thrombocytopenia, bone marrow vacuolization in myeloid and erythroid precursor cells; Molecular analysis^#	CS, azacytidine, HSCT, IL-6i
Yao syndrome	NOD2 IV28 + 158 or R702W	AD (variable penetrance)	Fever, rash, uveitis, abdominal pain, diarrhea, arthritis, arthralgia, sicca-like features	Increased IM during disease flares. Spongiotic dermatitis on skin biopsy; Molecular analysis^#	CS, TNFi, IL-1i
PFAPA	-----*	-----*	Fever, aphthosis, stomatitis, pharyngitis, and cervical adenitis, arthralgia, and myalgia	Increased IM during disease flares	CS, cimetidine, Colch, tonsillectomy, IL-1i
SAPHO syndrome	-----*	-----*	Synovitis, acne, palmoplantar pustulosis, sternocostoclavicular hyperostosis, osteitis, arthritis, uveitis, and conjunctivitis	Increased IM during disease flares	NSAID, CS, MTX, SSZ, bisphosphonate, TNFi
CRMO	-----*	-----*	Bone inflammation including localized skin redness (rare), warmth and/or swelling, and pain, palmoplantar pustulosis, acne and sacroiliitis	Increased IM during disease flares	NSAID, CS, MTX, SSZ, bisphosphonate, TNFi
Adult-onset Still’s disease	-----*	-----*	Fever, salmon-pink rash, arthritis, sore throat, pharyngitis, lymphadenopathy, serositis, hepatosplenomegaly, myocarditis	Increased IM during disease flares. Leukocytosis with neutrophilia; Increase in ferritin levels, positive biomarkers for MAS in severe cases; RF and ANA negative	CS, NSAID, MTX, CsA, IL-1i, TNFi, IL-6i
Schnitzler syndrome	-----*	-----*	Fever, chronic urticarial rash, arthralgia, arthritis, lymphadenopathy, bone pain (periostitis), hepatosplenomegaly	Increased IM during disease flares. Increased IgM or IgG immunoglobulin levels, neutrophilia, neutrophilic dermal infiltrate on skin biopsy	CS, IL-1i, IL-6i

AD autosomal dominant, AR autosomal recessive, CAPS cryopyrin-associated autoinflammatory syndromes, Colch colchicine, CRMO chronic recurrent multifocal osteomyelitis, CS corticosteroids, CsA cyclosporine, FCAS familial cold autoinflammatory syndrome, FMF familial mediterranean fever, HSCT hematopoietic stem cell transplantation, IL-1 interleukin-1, IL-1i interleukin-1 inhibitors, IL-6 interleukin-6, IL-6i IL-6 inhibitors, IgD immunoglobulin D, IgM immunoglobulin M, IM inflammatory markers (erythrocyte sedimentation rate, c-reactive protein and serum amyloid A), MEFV mediterranean fever gene, MKD mevalonate kinase deficiency, MVK mevalonate kinase gene, NLRP3 NLR family pyrin domain containing 3, NOD2 Nucleotide Binding Oligomerization Domain Containing 2, NOMID/CINCA neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular, NSAID non-steroidal anti-inflammatory drugs, MAS macrophagic activation syndrome, MTX methotrexate, MWS Muckle–Wells syndrome, PAAND pyrin-associated autoinflammation with neutrophilic dermatosis, PFAPA periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis, SAA serum amyloid A, SAPHO syndrome synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome, SSZ sulfasalazine, TNF tumor necrosis factor, TNFi TNF inhibitors, TNFRSF1A tumor necrosis factor receptor superfamily, member 1A, TRAPS tumor necrosis factor receptor-associated periodic syndrome, UBA1 ubiquitin like modifier activating enzyme 1, VEXAS syndrome vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome
^#Molecular analysis (sanger, next generation sequencing, whole exome sequencing)
----*no single gene or inheritance has been identified

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ISSN: 2523-3106

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