Table 2.

Baseline and annual evaluations

SystemBaselineRoutine monitoringSituational
Rheumatologic Autoantibodes (ANA, Sm, RNP, SSA, SSB, APL Abs ANCA, RF, and CCP)
Mandatory disease activity markersa: ESR, CRP, C3/C4
Facultative disease activity markersa: S100A8/9, S100A12, SAA. CXCL9, IL-18, sIL2R, IFN signature (nanostring, four-gene panel, monocyte CD169/CD274) 
At least annually:
Mandatory disease activity markersa: ESR, CRP, and C3/C4
Facultative disease activity markersa: S100A8/9, S100A12, SAA, IL18, CXCL9, sIL2R, and IFN signature (nanostring, four-gene panel, monocyte CD169/CD274) 
Plasma cytokines
Imaging of affected joints
CK, aldolase
Additional autoantibodies (myositis, scleroderma related) 
Dermatologic Skin exam and symptom screen by primary provider At least annually: Skin exam, symptom screen Skin biopsy 
Dental/oral health Symptom screen At least annually: Symptom screen Salivary flow measurement
Salivary gland imaging
MSG biopsy
Dental evaluation (unusual caries) 
Neurologic Symptom screen At least annually: Symptom screen CNS: Brain MRI, MRA, MRV, and LP
PNS: EMG ± biopsy, comprehensive neuropsychiatric testing 
Ophthalmologic Comprehensive eye exam, slit lamp, retinal, tear film staining At least annually: Comprehensive eye exam Uveitis, scleritis, episcleritis, vasculitis, and dry eye disease 
Cardiac Symptom screen At least annually: Symptom screen Myocarditis: Cardiac MRI, cardiac PET, cardiac catheterization, cardiac enzymes, lipids, TTE, and EKG 
Pulmonary Symptom screen At least annually: Symptom screen PFTs, CXR, HRCT chest, bronchoscopy, and VATS 
Gastrointestinal (In addition to general tests)
Hepatic panel, fecal calprotectin
Fib4 score 
At least annually: Hepatic panel, Fib4 score
As needed: Calprotectin 
Micronutrient levels
EGD
Enteroscopy
Colonoscopy
Abdominal imaging (CT and US)
Autoimmune hepatitis serologies
Celiac screen 
Renal (In addition to general tests) BMP (serum electrolytes, BUN, and Cr)
UA and UPCR 
At least annually: UA, UPCR, and BMP If concern for CKD: Renal US and kidney biopsy 
Endocrine Growth curves, TSH, free T4
Antithyroid Abs
A1C 
At least annually: Growth curves (for children), TSH, free T4
Situational: A1c, fasting glucose, and antithyroid Abs 
DEXA scan
T1DM-related autoantibodies 
Hematologic and oncologic CBC with differential, PT/PTT,
iron, and B12
APL Abs, cancer screening 
At least annually: CBC with diff, cancer screening (age appropriate)
As needed: PT/PTT,
Iron, B12
APL Abs 
Anti-IF antibodies
Anti-PLT antibodies
DAT, Coombs
SPEP, UPEP, IEP, and K/L FLC
Bone marrow biopsy, PET-CT 
Allergic and immunologic Quantitative immunoglobulins
T/B/NK subsets
Vaccine titers
Annual vaccinations 
At least annually: Quantitative immunoglobulins, T/B/NK subsets
Annual vaccinations
As needed: Vaccine titers 
IgG subsets
B cell subsets
T cell subsets
Anti-cytokine antibodies 
SystemBaselineRoutine monitoringSituational
Rheumatologic Autoantibodes (ANA, Sm, RNP, SSA, SSB, APL Abs ANCA, RF, and CCP)
Mandatory disease activity markersa: ESR, CRP, C3/C4
Facultative disease activity markersa: S100A8/9, S100A12, SAA. CXCL9, IL-18, sIL2R, IFN signature (nanostring, four-gene panel, monocyte CD169/CD274) 
At least annually:
Mandatory disease activity markersa: ESR, CRP, and C3/C4
Facultative disease activity markersa: S100A8/9, S100A12, SAA, IL18, CXCL9, sIL2R, and IFN signature (nanostring, four-gene panel, monocyte CD169/CD274) 
Plasma cytokines
Imaging of affected joints
CK, aldolase
Additional autoantibodies (myositis, scleroderma related) 
Dermatologic Skin exam and symptom screen by primary provider At least annually: Skin exam, symptom screen Skin biopsy 
Dental/oral health Symptom screen At least annually: Symptom screen Salivary flow measurement
Salivary gland imaging
MSG biopsy
Dental evaluation (unusual caries) 
Neurologic Symptom screen At least annually: Symptom screen CNS: Brain MRI, MRA, MRV, and LP
PNS: EMG ± biopsy, comprehensive neuropsychiatric testing 
Ophthalmologic Comprehensive eye exam, slit lamp, retinal, tear film staining At least annually: Comprehensive eye exam Uveitis, scleritis, episcleritis, vasculitis, and dry eye disease 
Cardiac Symptom screen At least annually: Symptom screen Myocarditis: Cardiac MRI, cardiac PET, cardiac catheterization, cardiac enzymes, lipids, TTE, and EKG 
Pulmonary Symptom screen At least annually: Symptom screen PFTs, CXR, HRCT chest, bronchoscopy, and VATS 
Gastrointestinal (In addition to general tests)
Hepatic panel, fecal calprotectin
Fib4 score 
At least annually: Hepatic panel, Fib4 score
As needed: Calprotectin 
Micronutrient levels
EGD
Enteroscopy
Colonoscopy
Abdominal imaging (CT and US)
Autoimmune hepatitis serologies
Celiac screen 
Renal (In addition to general tests) BMP (serum electrolytes, BUN, and Cr)
UA and UPCR 
At least annually: UA, UPCR, and BMP If concern for CKD: Renal US and kidney biopsy 
Endocrine Growth curves, TSH, free T4
Antithyroid Abs
A1C 
At least annually: Growth curves (for children), TSH, free T4
Situational: A1c, fasting glucose, and antithyroid Abs 
DEXA scan
T1DM-related autoantibodies 
Hematologic and oncologic CBC with differential, PT/PTT,
iron, and B12
APL Abs, cancer screening 
At least annually: CBC with diff, cancer screening (age appropriate)
As needed: PT/PTT,
Iron, B12
APL Abs 
Anti-IF antibodies
Anti-PLT antibodies
DAT, Coombs
SPEP, UPEP, IEP, and K/L FLC
Bone marrow biopsy, PET-CT 
Allergic and immunologic Quantitative immunoglobulins
T/B/NK subsets
Vaccine titers
Annual vaccinations 
At least annually: Quantitative immunoglobulins, T/B/NK subsets
Annual vaccinations
As needed: Vaccine titers 
IgG subsets
B cell subsets
T cell subsets
Anti-cytokine antibodies 

ANA, antinuclear antibody; Sm, Smith; RNP, ribonucleoprotein; APL, antiphospholipid; ANCA, antineutrophil cytoplasmic antibody; RF, rheumatoid factor; CCP, cyclic citrullinated peptide; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; SAA, serum amyloid A; IL, interleukin; sIL2R, soluble IL-2 receptor; IFN, interferon; CK, creatine kinase; MSG, minor salivary gland; MRI, magnetic resonance imaging; MRA, magnetic resonance angiography; MRV, magnetic resonance venography; LP, lumbar puncture; EMG, electromyography; PET, positron emission tomography; TTE, transthoracic echocardiogram; EKG, electrocardiogram; PFT, pulmonary function test; CXR, chest x-ray; HRCT, high resolution computed tomography; VATS, video assisted thoracoscopic surgery; EGD, esophagogastroduodenoscopy; US, ultrasound; BMP, basic metabolic panel; BUN, blood urea nitrogen; Cr, creatinine; UA, urinalysis; UPCR, urine protein:creatinine ratio; CKD, chronic kidney disease; TSH, thyroid-stimulating hormone; DEXA, dual energy x-ray absorptiometry; T1DM, type 1 diabetes mellitus; CBC, complete blood count; PT, prothrombin time; PTT, partial thromboplastin time; IF, intrinsic factor; PLT, platelet; DAT, direct antigen test; SPEP, serum protein electrophoresis; UPEP, urine protein electrophoresis; IEP, immunoelectrophoresis; K/L FLC, κ/λ-free light chain; IgG, immunoglobulin G.

a

Mandatory vs. facultative disease activity markers: We recommend checking broadly available disease activity markers (labeled “mandatory”) for all patients with HA20. Other disease activity markers (labeled “facultative”) may be available only at selected diagnostic immunology labs. However, we have seen patients with active organ-threatening disease (i.e., liver disease and neuroinflammation) who have normal standard disease activity markers but elevated facultative disease activity markers. We therefore check both mandatory and facultative markers annually in all patients.

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