New Adult Clinical

Autoinflammatory Disease Case

Qingping Yao, MD, PhD

Senior Staff

Department of Rheumatic and Immunologic Diseases

Cleveland Clinic

Cleveland, OH

Case presentation

A 45-year old white F

Recurrent erythematous rash 1 yr

Rash lasted 3 to 7 days and disappeared for 1 to 2 days

Photo: erythematous plaques and patches

Spongiotic dermatitis

Case, cont’d

Recurrent morning swelling, pain, and weakness in

the hands and feet, rarely forearms and knees

Recurrent blurred vision

3 to 7 days/episode. Severe abdominal pain lasting

about 2 hours AM

She denied fevers.

Case, cont’d

ROS: wt loss, night sweats, and dry mouth, IBS type.

FH: negative

Born in Wales and married with healthy 2 children.

PE: skin changes, otherwise negative

Labs

CBC, CMP, UA all wnl

ESR, serology, CK and aldolase wnl

EGD and Colonoscopy negative

Ophthal exam: normal

Lip minor salivary gland bx: negative

DDX

FMF

TRAPS

Blau’s syndrome

NAID

Genetic testing

NOD2 gene mutation: heterogygous

IVS8+158, R702W

TNFRSF1A for TRAPS: negative

NOD2-associated autoinflammatory

disease (NAID)

Newly reported disease

White adult onset mostly

Phenotype:

-Periodic fever, dermatitis and polyarthritis

-Features: Spongiotic dermatitis and pedal swelling

Genotype: NOD2 variants: IVS8+158, R702W and R703C

Characteristics of Cumulative Clinical and

Laboratory Manifestations of NAID Patients

Positive NOD2

Variable patients (n=22)

Gender (Female/Male) 13/9

Mean age at diagnosis (range, years) 40.1 (17-72)

Mean disease duration (range, years) 4.7 (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 20/22 (90.9%)

Gastrointestinal 13/22 (59.1%)

Serositis/chest pain 5/22 (22.7%)

Sicca-like 9/22 (40.9%)

Pulmonary 3/22 (13.6%)

Uveitis 0/22 (0%)

Raised ESR/CRP 9/20 (45.0%)

ESR, erytherocyte sendimentation rate; CRP, C-reactive protein

NOD2 gene

Pathogenesis of NAID

Interaction: gene mutations+environment (GI

stress, trauma)

Cytokines: Th1/Th2 might not play a role. IL-

17 and some type of T cells may contribute

Under investigation

Therapy and Prognosis for NAID

Depends on signs and symptoms

Topical steroids

Small dose of prednisone

Sulfasalazine

Biologics

Patients appear to run benign and intermittent course; some have nearly persistent polyarthritis, fatigue, rash, and fever

References Yao Q, et al. A new category of autoinflammatory disease associated with NOD2

gene mutations. Arthritis Res Ther. 2011;13(5):R148. doi: 10.1186/ar3462. Epub

2011 Sep 14.

Yao Q, et al. Dermatitis as a characteristic phenotype of a new autoinflammatory

disease associated with NOD2 mutations. J Am Acad Dermatol. 2013

Apr;68(4):624-31. doi: 10.1016/j.jaad.2012.09.025. Epub 2012 Oct 24.

Yao Q, et al. Granulomatous pneumonitis associated with adult-onset Blau-like

syndrome. Am J Respir Crit Care Med. 2012 Sep 1;186(5):465-6.

Yao Q. Nucleotide-binding oligomerization domain containing 2: Structure,

function, and diseases. Semin Arthritis Rheum. 2013 Jan 24. pii: S0049-

0172(12)00287-9. doi: 10.1016/j.semarthrit.2012.12.005. [Epub ahead of print]

Yao Q, et al. Distal lower extremity swelling as a prominent phenotype of NOD2-

associated autoinflammatory disease. Rheumatol (Oxford), 2013 Apr 12. [Epub

ahead of print]