Connective tissue disorders

Terms in this set (21)

This is a multi system, autoimmune chronic inflammatory condition that can affect any tissue and organ of the body ~ skin, joints, kidney ( glomerular nephritis), synovial membranes ( pericardial or pleural effusions), blood vessels
-> disease has a fluctuating course w/ remissions and exacerbations

Epidemiology:
- MC rheumatic disease
- African Americans
- Females of childbearing age ( disease onset 16-55y/o

Etiology:
- 20% more likely to develop if sibling also has it

Risks:
- Drugs- procainamide and hydrazine ( pts. who slowly metabolize acetylators)
- Horomones: OCPs
- Environmental triggers: UV sunlight (MC) , infectious or endogenous viruses ( EBV)

Pathophysiology:
- Nucleic acids (DNA/RNA) are targeted by immune system
- dendritic cells to T cells activate -> B cells (plasma cells) produce antibodies by secreting cytokines:Interferon (IFN)- alpha associated w/ renal disease
- PMN's cause vascular damage and produce IFN: leads to early or accelerated atherosclerosis [MCC of death is CAD]
-> Considered CAD equivalent ( includes DM, atherosclerosis)
- SLE genetic variations impair clearance which causes immune complexes to deposit and cause tissue injury ( skin, kidney)
- activation of complement


Manifestations:
- 3 initial findings: butterfly ( malar) rash, joint pain, and fatigue [ common Sx. of MS)
- decreased photosensitivity, increased serositis: in MEN
- decreased malar rash, photosensitivity, purpura, alopecia, Raynauds phenomenon, renal and CNS involvement, increased serositis, pulmonary, sicca, and musculoskeletal manifestations

Dx.
- Takes 5yrs to dx. pts. w/ SLE
- developed and validated criteria for pts. w/ long-standing established disease American college or Rheumatology Combination of any 4 manifestations, serially or simultaneously during observation period:
o Malar rash ( skin Sx.)
o Discoid rash
o Photosensitivity rash
o + ANA
o Arthritis
o Serositis: pleuritis or percarditis
o oral ulcers
o renal disorder
o neurological disorder
o hematological disorder
o immunologic disorder- anti DS DNa, anti smith, anti phospholibid antibody
[Critique: over-exagerates skin manifestations]

DDx.: dermatomysitis, rheumatoid arthritis, Behcets disease, infection,

Management:
- Take Ca and Vit D (800 units) because @ risk osteoporosis and vertebral compression fractures
- Avoid sun, OCPs, or estrogen therapy
- Tx. early infections because immunocompromised pt.
- Fever, musculoskeletal sx., serositis: NSAIDs 1st line, short tapered dosage of steroids
- Hematological manifestations: Steroids 1st line
- Renal and other organ disease: immunosuppressants, high dose steroids, cyclophosphamide, methotrexate, renal dialysis, kidney transplant, control HTN ( ACEI)
- Monoclonal antibody ( B-cell stimulator specific inhibitor) decreases disease activity
- For flares: belimumab (Benlysta)


Prognosis:
- Infection and nephritis are major causes of mortality in all stages of SLE
- Thrombosis/ Atherosclerosis
- Malignancy: Non-Hodgkin's lymphoma, cervical and lung cancer MC
-> fever, weight loss, and lymphadenopathy
- Renal and CNS manifestations is poor prognosis ( lethal)
Variable Manifestations in SLE:

Systemic:
o Fever (low grade fever <101), anorexia, malaise, weight loss, *fatigue)
->R/o infection if fever @ 101.6 and SLE -> CBC would tell if increase WBC ( sign of infection), pancytopenia, chills

Skin, mucus membranes, and hair:
o Malar rash: spares nasolaboal folds, fixed erythema either flat or raised over malar eminences
o Discoid rash: erythematous raised patches, atrophic scarring in older lesions ( disfiguring)- MC on head ( neck and face)
o Photosensitivity
o Raynauds phenomenon
o painless (MC) or painful oral, nasopharyngeal or vaginal ulcers
-> R/o Behcets disease ( widespread mucosal ulcerations)

Muskuloskeletal/ arthritis:
o symmetric, non errosive arthritis of > 2 peripheral joints (hands, wrist, and knees) w/ warmth, tenderness, or effusion
-> R/o Rheumatoid arthritis: has bony erosions and involves > 2 peripheral joints
o Tenosynovitis: early manifestations of SLE, tendon rupture ( patella- can't extend knee, Achilles- can't plantar flex, biceps, triceps)
o Myositis

Renal:
o Proteinuria
o hematuria
o glomerulonephritis
o cellular casts ( RBC, grandular, tubular, mixed
o renal failure

Heart and vascular serositis:
o Pericarditis ( sharp, stabbing pain, leaning forward makes it better, pericardial friction rub, w/ diffuse ST elevations)
o Endocarditis, myocarditis
o Libman Sack's endocarditis: non bacterial verrucous valvular lesions ( mitral and tricuspid MC)
o Premature atherosclerosis

Pulmonary:
o Pleuritis: well localized, deep breath or coughing makes it worse, auscultating a pleural friction rub ( ask to hold breath), presence of pleural effusion- exudative ( pulmonary capillaries are inflamed)
o *PE: antiphospholipid syndrome and premature atherosclerosis, DVT

CNS:
o Psychosis, seizures ( MC - Grand Mal)
o Eye: inflammation of retinal artery or infarction from antiphospholipid syndrome

GI:
o peritonitis
o mesenteric vasculitis w/ intestinal infarction
o Pancreatitis
o IBD
o PUD

HEME: (think ITP caused by SLE) Pt. DOES NOT PRESENT W/ bleeding
o Pancytopenia: antiphospholipid antibody + -> antiphospholipid syndrome prolongs PTT and associated w/ thrombosis
o hemolytic anemia w/ reticulocytosis
o lymphopenia
o MCC of thrombocytopenia: autoimmune mediated
This is a systemic autoimmune disease characterized by:
- excessive deposition of collagen and other connective tissue macromolecules in skin and multiple internal organs
- Prominent and severe fibroproliferative alterations in microvasculature ( Pulmonary artery)
- Numerous humoral and cellular immunologic abnormalities

Epidemiology:
o MC in women
o 30-50y/o (MC)

Pathophysiology:
- initiated by unknown factor in a genetically receptive host triggers microvascular injury
-Hallmark: severe, often progressive fibroproliferative vasculopathy, exaggerated & widespread accumulation of fibrotic tissue
-vascular dysfunction is one of the earliest alterations of systemic sclerosis
- Immunologic alterations in innate and acquired immune responses

Type:
- Limited skin involvement: ( skin distal to elbows, knees, +/- face and neck)
o CREST SYNDROME: calcinosis, reynauds phenomenon, esophageal dysmotility, sclerodactyl, telangiectasias
- Diffuse systemic/skin sclerosis: severe and progressive internal organ involvement

Dx.
- ACR classification criteria
- ANA: SCREENING TEST
- Topoisomerase 1 antibodies (SPECIFIC): diffuse disease
- Anticentromere antibodies (SPECIFIC): limited disease
- GI studies for esophageal dysmotility
- Cadiopulmonary tests: CXR, ABG, pulmonary function test for pulmonary fibrosis, CxCL4 serum lvl (cytokines), NT-proBNP correlates w/ early pulmonary HTN, CT scan, EKG, echo
- Rapid rising creatine- Scleroderma renal crisis

Management:
- None approved FDA for disease modifying Tx.
- Pregnancy: increases risk of abortions and complications ( like pulmonary HTN)

Prognosis:
- MCC of death: scleroderma renal crisis, pulmonary HTN and pulmonary fibrosis
This is a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine organs: "Sicca Sx.:" xerophthalmia (dry eyes), xerostomia (dry mouth), and parotid gland enlargement

Epidemiology:
- MC in females
- 2nd MC rheumatic disorder to SLE
- 4th- 5th decade of life

Clinical manifestations:
- Sicca Sx.
o Xerophthalmia
o Xerostomia
o Parotid gland enlargement
- extraglandular findings:
o skin: purpura, urticaria
o arthritis
o Raynaud's phenomenon
o myalgia
o pulmonary
o kidney and GI disease
o LAD
o Cytopenias
o Neuropathy
o Vasculitis
o Xerodermia: dry skin

DDx.
- ( R/o Mumps and bulemia- thin female)

Dx.
- Criteria accepted by American College of Rheymatology (ACR) [ Dx. requires > 4 of criteria + either criterion 5 or 6]
1.) Ocular Sx.: dry eyes for 3 months (sand, gritty eyes w/o Hx. of something getting into eyes)
2.)Oral Sx. dry mouth, recurrently swollen salivary hands ( pt. has to use liquids to aid in swallowing)
3.) Ocular signs: Schimer test performed w/o anesthesia (<5 mm in 5min is positive result)
4.) Oral signs: abnormal salivary scintigraphy findings, abnormal parotid sialography findings, abnormal sialometry findings
5.) + minor salivary gland biopsy findings
6.) + anti- SSA or anti- SSB antibody results
[ Exclusion criteria: head and neck irradiation, HCV, AIDS, Prior lymphoma, Sarcoidosis, GVHD, use of anticholinergic drugs]

Tx.
- lotion for dry skin
- artificial tears for dry eyes
-> cyclosporine is 1st line if artificial tears don't work
- rituximab: extraglandular Sx.

Complications:
o pregnant pts. w antiRo/ SS- A antibodies are @ risk for fetal loss, complete heart block in fetus, neonatal lupus
o incidence of Non-Hodgkin lymphoma
-> MALT is MC type


Prognosis: malignancy w/ rheumatoid disorder presence of lymphoma: non-Hodgkins