Connective Tissue Disorders
Theresa Coyner
Karen Congelio
Katrina Nice Masterson
OBJECTIVES
After studying this chapter, the reader will be able to:
Identify and differentiate the most common connective tissue disorders.
Discuss treatment modalities for the most common connective tissue disorders.
List several important patient education aspects for each disorder.
Provide a list of patient resources on connective tissue disorders.
KEY POINTS
Early diagnosis and treatment may significantly slow the connective tissue disease process and increase patient’s quality of life.
A complete physical exam and physiological assessment should be completed if a collagen vascular disease is suspected due to possible misdiagnosis and to capture any central nervous system involvement.
Patient education and support are vital to treatment compliance.
Encourage patients to join support groups and organizations.
OVERVIEW
Connective tissue disorders (collagen vascular disease) are defined as a group of acquired disorders that have the commonality of immunologic and inflammatory changes in small blood vessels and connective tissue. Common features may include arthritis, skin lesions, iritis and episcleritis, pericarditis, pleuritis, subcutaneous nodules, myocarditis, vasculitis, and nephritis. Lupus, scleroderma, and myositis will be discussed in this chapter.
I. LUPUS ERYTHEMATOSIS
A. Definition: Lupus is a chronic autoimmune disease resulting in inflammation and tissue damage. The name “lupus,” Latin for wolf, was coined in the 10th century possibly because the lesions resembled wolf bites.
B. Etiology
1. The exact cause of lupus is unknown; however, current research points to interrelated immunologic, environmental, hormonal, and genetic factors.
2. Of the babies born with neonatal lupus erythematosus (NLE), 98% were reported to have anti-Ro antibodies and approximately one third with La antibodies. These IgG antibodies pass from the placenta to the fetus.
3. Recent studies are looking at chromosome 1 for a genetic link; however, only 10% of lupus patients will have a close relative with lupus. About 5% of children born to individuals with lupus will develop the disease.
4. Often called a “woman’s disease,” lupus strikes women 10 to 15 times more frequently than men and occurs most often during childbearing years.
5. Although the disease occurs worldwide, it is most prevalent in persons with African, American Indian, and Asian origins.
C. Symptoms
1. Arthralgia
2. Fever greater than 100°F
3. Arthritis
4. Prolonged or extreme fatigue
5. Skin rashes
6. Anemia
7. Kidney involvement
8. Pleurisy
9. Butterfly-shaped (malar) rash across the cheeks and nose
10. Less frequent occurring symptoms include photosensitivity, hair loss, mouth or nose ulcers, abnormal blood clotting problems, Raynaud phenomenon, and seizures.
D. Types of lupus
1. Cutaneous lupus erythematosus has many different types including:
a. Chronic cutaneous lupus erythematosus (CCLE)
(1) The most common form of CCLE is discoid lupus erythematosus (DLE).
(a) DLE lesions are often erythematous, scaly, and thickened and may produce scarring or discoloration of the skin; usually painless and nonpruritic.
(b) Localized DLE: lesions limited to the head (possible alopecia), ears, and neck (Figures 19-1 and 19-2).
(c) Generalized DLE: lesions present anywhere on skin.
(d) Long-standing lesions are at risk for skin cancer.
 FIGURE 19-1. Chronic cutaneous lupus erythematosus (CCLE) causing scarring alopecia. (From Goodheart, H. P. (2003). Goodheart’s photoguide of common skin disorders (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.) |
(2) Hypertrophic (thickened) or verrucous (wartlike) lupus erythematosus (LE)
(3) Lupus profundus: DLE lesions occurring in conjunction with firm lumps in the fatty tissue (panniculitis) (Figure 19-3)
(4) Mucosal DLE: lesions that occur in mucous membranes of the mouth, nose, and eyes
(5) Chilblain lupus: lesions consisting of red to purplish papules that usually occur on the toes and fingers
b. Subacute cutaneous lupus erythematosus (SCLE)
(1) Papulosquamous: erythematous plaques
(a) May resemble psoriasis
(b) Most common on sun-exposed areas of the arms, shoulders, neck, and trunk; face less frequently involved
(2) Erythemic annular lesions with no scale (LE tumidus)
(3) Both forms are photosensitive to natural and artificial light.
 FIGURE 19-2. Discoid lupus erythematosus (DLE). (From Edward, S., & Yung, A. (2011). Essential dermatopathology. Philadelphia, PA: Wolters Kluwer.) |
 FIGURE 19-3. Lupus profundus (lupus panniculitis). (From Elder, D. E. (2012). Atlas and synopsis of Lever’s histopathology of the skin. Philadelphia, PA: Wolters Kluwer.) |
(4) Lesions usually do not scar but may cause discoloration of skin.
c. Acute cutaneous lupus erythematosus (ACLE)
(1) Produces flat erythemic areas resembling sunburn, which can be transient, lasting several days to weeks (Figure 19-4).
(2) Localized ACLE involves both cheeks and nose presenting as a butterfly-shaped malar rash.
(3) Generalized ACLE presents with a maculopapular eruption representing a photosensitive dermatitis.
2. Systemic lupus erythematosus (SLE) attacks multiple systems in the body, which may include the skin (classic butterfly-shaped malar rash most common), liver,
joints, lungs, blood vessels, heart, kidneys, liver, brain, and nervous system. SLE can have significant morbidity and potential mortality when associated with acute lupus erythematous as a manifestation (Box 19-1).
joints, lungs, blood vessels, heart, kidneys, liver, brain, and nervous system. SLE can have significant morbidity and potential mortality when associated with acute lupus erythematous as a manifestation (Box 19-1).
 FIGURE 19-4. Acute cutaneous lupus erythematosus (ACLE) maculopapular eruption in a photosensitive pattern. (From Knight, L. (2013). Medical terminology: An illustrated guide. Philadelphia, PA: Wolters Kluwer.) |
3. Drug-induced lupus may develop after taking certain medications. Symptoms usually resolve weeks to months after discontinuation of the drug (Figure 19-5).
4. Neonatal lupus erythematosus
a. NLE is rare.
b. Occurs in neonates with transplacentally acquired maternal anti-Ro (SS-A) and/or anti-La (SS-B) antibodies.
c. Manifestations may include:
(1) Congenital heart block
(2) Cutaneous lesions
(3) Liver disease
(4) Thrombocytopenia
E. Lupus as a disease continuum
1. CCLE is seen as the mild end of the spectrum with only localized lesions.
2. SCLE presents with mild SLE.
3. Active SLE with internal organ involvement (possible death), with or without skin lesions, is at the far end of the disease spectrum.
F. Diagnosis
1. A complete history and physical should be performed, including a full-skin assessment.
2. Currently, there is no single definitive laboratory test for lupus.
Box 19-1. Criteria for the Diagnosis of Systemic Lupus Erythematosus
Patient must meet four of the following criteria, including at least one immunologic criterion and at least one clinical criterion; or the patient has biopsy-proven nephritis compatible with systemic lupus in the presence of either antinuclear antibody or anti-double-stranded deoxyribonucleic acid.
Clinical criteria
Oral lesions
Nonscarring alopecia
Synovitis of the joints
Serositis of the lining around organs
Renal involvement
Neurological involvement
Hemolytic anemia
Leukopenia
Thrombocytopenia
Immunologic criteria
Elevated antinuclear antibodies
Elevated anti-double-stranded deoxyribonucleic acid
Anti-Smith antibodies
Antiphospholipid antibodies
Low complement
Direct Coombs (antiglobulin) test in the absence of hemolytic anemia
Adapted from Petri, M., Orbai, A. M., Alarcon, G. S., Gordon, C., Merrill, J. T., Fortin, P. R., …, Magder, L. S. (2012). Derivation and validation of systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis and Rheumatology, 64(8), 2677-2686.
 FIGURE 19-5. Drug-induced cutaneous lupus. (From Elder, D. E. (2014). Lever’s histopathology of the skin. Philadelphia, PA: Wolters Kluwer.) |
3. Lupus symptoms can mimic other illnesses and are often vague and transient, resulting in misdiagnosing and underdiagnosing of lupus.
4. The American College of Rheumatology and the Systemic Lupus International Collaborating Clinics issued a list of criteria to assist the practitioner in diagnosing SLE and to establish consistency for epidemiologic surveys (Box 19-1).
G. Pregnancy and lupus
1. There is no reason why a woman with lupus should not become pregnant, unless she has organ involvement.
2. There is risk of disease activity during and 3 to 4 weeks after pregnancy; therefore, she should be monitored closely.
3. Many persons with lupus have antiphospholipid antibodies, which affect coagulation factors and are associated with miscarriage.
H. Diagnostic testing may include:
1. CBC with differential.
2. Platelet count.
3. Erythrocyte sedimentation rate.
4. Serum electrophoresis.
5. Antinuclear antibodies (ANA) and LE cell tests
6. Anti-double-stranded deoxyribonucleic acid (antidsDNA) antibody: this is the most specific test for lupus and correlates with disease activity.
7. Urine studies.
8. C3 and C4 serum studies
9. Chest x-rays.
10. Skin biopsy for H&E. If not definitive, skin biopsy for direct immunofluorescence.
11. Lupus anticoagulant and anticardiolipin tests.
I. Treatment
1. Prevention is key to minimizing symptoms, reducing inflammation, and maintaining normal bodily functions.
a. Avoid sun exposure/wear sunscreen to prevent rashes.
b. Exercise regularly to prevent muscle weakness and fatigue.
c. Participate in support groups and/or counseling to reduce stress.
d. Eliminate negative habits, such as smoking, drinking, etc.
e. Avoid artificial light sources, such as tanning beds.
2. Treatment is individualized and based upon presenting symptoms.
3. Treatments may include:
a. Nonsteroidal anti-inflammatory drugs (NSAIDs).
b. Acetaminophen.
c. Corticosteroids (topical, systemic, or intralesional). Ultrapotent topical corticosteroids may be indicated even on the face.
d. Topical immunomodulators such as pimecrolimus and tacrolimus.
e. Antimalarials.
(1) Hydroxychloroquine sulfate. Usual dose 200 mg one to two times daily. Dosage generally should not exceed 6.5 mg/kg/daily.
(2) Chloroquine phosphate. Usual dose is 250 mg one to two times daily.
(3) Quinacrine hydrochloride. Usual dose is 100 mg one to two times daily.
(4) All antimalarials may cause eye toxicities. Patients should have eye examinations by optometrist/ophthalmologist every 6 months.
4. Extensive or persistent cutaneous disease
a. Oral prednisone, oral retinoids, methotrexate, thalidomide, and azathioprine have all been utilized.
5. Systemic disease will be treated by rheumatology.
a. Prednisone, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, interferon, leflunomide, TNF alpha inhibitors, CD4 monoclonal antibodies, and bone marrow transplant have all been utilized.
6. Specific treatment for systemic disease involving organ may include antihypertensive medications, dietary changes to reduce hypertension, anticoagulants, and dialysis and or kidney transplant for renal failure.
PATIENT EDUCATIONLupus Erythematosus
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