Guideline for Connective Tissue Disease
Suggestive Symptoms to Connective Tissue Disease
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1. Skin Rash – Malar, discoid rash, photosensivity
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2. Swelling of joints - mono/oligo(3~5)/poly (>5)
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3. Serositis –Presence of pericardial or pleural effusion of
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4. Seizures – unknown etiology or offending drugs
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5. Psychosis – unknown etiology or offending drugs
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6. Fever –
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7. Fatigue – Weakness of extremities, especially
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8. Myalgia/myositis – nonspecific muscle pain
unknown infection focus or
unknown etiology.
malignancy
Suggestive Physical Findings to Connective Tissue Disease
• Alopecia, hair loss
• Dry eyes
• dry mouth, Oral/nasal ulcers
• Vasculitic lesions, Adenopathy
• Edema
• Cyanosis of fingers in cold weather or during emotional stress
Initial Serological Evaluation with Antinuclear Antibody
• If ANA negative – Symptoms remit, SLE not present
• If ANA negative – Symptoms persists,
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- repeated ANA
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- check other markers (Rheumatic factor)
• If RF negative – Check HLA-B27, Study Sero-negative Arthropathy
(Ankylosing Spondylosis, Reiter’s syndrome, Psoriatic Arthritis)
• If RF positive – consider as ANA positive, also
study disease associated
with RF.(See after)
Diseases Commonly Associated with Positive Rheumatoid Factor
• Rheumatic diseases
• Rheumatoid arthritis, systemic lupus erythematosus,
connective tissue disease,
scleroderma, mixed
Sjogren's syndrome
• Viral infections
• Acquired ImmunoDeficiency Syndrome, hepatitis, mononucleosis, influenza,
ers; after
vaccination (may yield falsely elevated titers of antiviral
antibodies)
• Parasitic infections
• Trypanosomiasis, kala-azar, malaria, schistosomiasis, filariasis
• Chronic bacterial infections
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Tuberculosis, leprosy, yaws, syphilis, brucellosis, subacute bacterial
endocarditis, salmonellosis
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Neoplasms
After irradiation or chemotherapy
Other hyperglobulinemic states
Hypergammaglobulinemic purpura, cryoglobulinemia, chronic liver disease,
sarcoid, other chronic pulmonary diseases
Initial Serological Evaluation with Antinuclear Antibody
• If ANA positive, consider diseases below before diagnosis of SLE
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- Check CPK, EMG, NCV, muscle/skin biopsy
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for DermatoMyositis/PolyMyositis
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- Survey Systemic Sclerosis(Scleroderma), CREST
- Mixed Connective Tissue Disease (Anti-RNP)
- Drug-induced lupus
- Sjogren’s syndrome
If ANA positive, with no symptom, or only one or two symptoms that are
suggestive of connective tissue disease
- Undifferentiated Connective Tissue Disease(UCTD)
Laboratory investigations for Connective Tissue Disease
• Urine Routine – proteinuria > 3+, Daily protein >0.5g. CCR
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Complete Blood Count & Differential Count, platelet
– hemolytic anemia, leukocytopenia, thrombocytopenia
– if agranulocytosis, consider drug-induced.
E.S.R, CRP – acute phase reactant, follow-up of disease activity, CRP to rule
out infection.
Glucose, Bun, Cr, Na, K – Renal Function Test
Bil(T/D), GOT/GPT – liver function, autoimmune hepatitis
Lipid profile – Triglyceride, Cholesterol in nephrotic syndrome
Albumin
– edema/proteinuria/nephrotic syndrome
• PT/APTT – Prolonged time even mixed with normal serum.
• RPR
– false positive indicates presence of antiphospholipid antibody
• Anti-dsDNA – related with lupus nephritis
• ENA-screening(Anti-SM, Anti-RNP,Anti-SSA/SSB)
• Anticardiolipin Ab, Lupus Anticoagulant
How to Establish A Diagnosis
• What is Criteria for CTD? Classification rather than Diagnosis
• Evaluation of System:
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- mucocutaneous subacute cutaneous LE, Discoid LE
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- musculoskeletal: lupus myositis, lupus arthritis
- kidney: lupus nephritis
- heart & vessels: lupus pericarditis, atherosclerosis, Antiphospholipid
syndrome
• - Stomach system: lupus vasculitis of intestine
• - Brain: CNS lupus
Condition That may confused with systemic lupus erythematosus
• Undifferentiated connective tissue disease
• Sjogren’s syndrome
• Antiphospholipid antibody syndrome
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Fibromyalgia with positive antinuclear antibody
Idiopathic thrombocytopenia purpura
Drug-induced lupus
• Early rheymatoid arthritis
• Vasculitis
Evaluation of patient’s condition
• 1. Infection
• 2. Drug-related complication
• 3. Disease flare-up
Infection
• Always rule out infection first in febrile patient with confirmed connective
tissue disease.
• Detail physical examination
• Infection study including blood culture, Chest X-ray, U/A, Sonography of
abdomen, CSF-study, cellulitis.
• Aggressive antibiotic treatment if condition deteriorated and sepsis is highly
suspected.
Recommended monitoring strategy for drugs commonly used in SLE
Drug
Toxicities requiring monitoring
System review
Laboratory
Baseline evaluation
Salicylates,nonSteroidal antiinflammatory
drugs
Gastrointestinal
bleeding,hepatic
toxicity,
renal toxicity,
hypertension
CBC, creatinine,
urinalysis, AST,
ALT
Dark/black
CBC yearly,
stool,dyspepsia, creatinine
nausea/vomiting, yearly
abdominal pain,
shortness of
breath, edema
Glucocorticoids infections,
Hypertension,
hyperglycemia,
hyperlipidemia,
hypokalemia,
osteoporosis,
avascular
necrosis, cataract,
weight
gain, Fluid
retention
Hydroxy-chloro Macular damage
quine
Drug allergy
BP,glucose,
Polyuria,
Urinary dipstick
potassium,
cholesterol,
bone densitometry
triglycerides
(HDL, LDL)
polydipsia,
edema, shortness
of breath, BP at
each visit, visual
changes, bone
pain
for glucose
every
3–6 months,
total
cholesterol
yearly,
bone
densitometry
yearly to assess
osteoporosis
None unless
patient is
over 40 years of
Visual changes
Funduscopic
and
visual fields
age or has previous
eye disease
every
6–12 months
Drug
Toxicities requiring monitoring
System review
Baseline evaluation
Laboratory
Azathioprine
Myelosuppression, CBC, platelet
Symptoms of
CBC and
hepatotoxicity,
count,creatinine,
lymphoproliferative AST or ALT
Disorders
pancreatitis
myelosuppression platelet count
every 1–2
weeks with
changes in dose
(every
1–3 months
thereafter),
AST yearly, Pap
test
at regular
intervals
Cyclophosphamide
Myelosuppression, CBC and DC and
myeloproliferative platelet count,
disorders,
urinalysis
malignancy,
immunosuppression
,
hemorrhagic
Symptoms of
CBC and
myelosuppression urinalysis
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monthly, urine
hematuria,
cytology and
Infertility
Pap test
yearly for life
cystitis,
secondary infertility
Methotrexate
Myelosuppression,
hepatic fibrosis,
cirrhosis,
pulmonary
infiltrates, fibrosis
CBC, CXR within
past year, hepatitis
B, C serology in
high-risk patients,
AST, albumin,
bilirubin,
Creatinine
Symptoms of
CBC and
myelosuppression platelet count
,
every 4–8
shortness of
weeks, AST
breath,
or ALT every
nausea/vomiting, 4–8
oral ulcer
weeks, albumin
every
4–8 weeks,
serum
creatinine,
urinalysis
Evaluate Disease Activity
• Clarify Life-threatening and not life-threatening condition
• (1) Mild, not organ or life-threatening
• (2) Impairs quality of life but not organ or life threatening
• (3) Severe disease, organ or life threatening, potentially reversible
Serious and Life-Threatening Manifestations of SLE: Responses to Glucocorticoids
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Vasculitis
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Severe dermatitis of subacute cutaneous LE or SLE
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Polyarthritis
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Polyserositis--pericarditis, pleurisy, peritonitis
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Myocarditis
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Lupus pneumonitis
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Glomerulonephritis--proliferative forms
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Hemolytic anemia
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Thrombocytopenia
Diffuse CNS syndrome --acute confusional state, demyelinating syndromes,
intractable headache
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Serious cognitive defects
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Myelopathies
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Peripheral neuropathies
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Lupus crisis
Manifestations not often responsive to glucocorticoids
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Thrombosis--includes strokes
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Glomerulonephritis--scarred end-stage renal disease, pure membranous
glomerulonephritis
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Resistant thrombocytopenia or hemolytic anemia--occurs in a minority of
patients; consider splenectomy, cytotoxics, danazol, or cyclosporine/neoral
therapies
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Psychosis related to conditions other than SLE, such as glucocorticoid
therapy
Manifestations of SLE That Can Be Managed with Strategies Other Than
Immunosuppression
• Thrombosis
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Recurrent fetal loss with antiphospholipid
Thrombocytopenia or hemolytic anemia
Seizures without other serious manifestations
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Behavior disorders or psychosis without other serious manifestations
Pure membranous glomerulonephritis