Sec 27 The Skin in Vascular and Connective Tissue and Other Autoimmune Disorders Flashcards
Identified as a candidate gene responsible for the development of autoimmune diseases; a transcription factor that regulates the ectopic expression of proteins, normally expressed in peripheral tissues, in the thymus, allowing for thymic expression of the latter and subsequent negative selection of self-reactive thymocytes before they migrate as mature T cells to the secondary lymphoid organs such as the spleen and lymph nodes.
Autoimmune regulator (AIRE) gene
Expressed on T cells providing an inhibitory signal upon their activation; also expressed on other immune cells including B cells and myeloid cells; encoded by the PDCD1 gene, with a SNP in its fourth intron associated with autoimmunity, including SLE and RA.
Programmed cell death 1 (PD-1)
Second most frequent clinical manifestation of LE after joint inflammation
Skin disease
The most common form of Chronic Cutaneous Lupus Erythematosus
Discoid Lupus Erythematosus
Fixed erythema, flat or raised, over the malar eminences, tending the spare the nasolabial folds
Malar rash
Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions
Discoid rash
Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation
Photosensitivity
SLE: Oral ulcers
Oral or nasopharyngeal ulceration, usually painless, observed by a physician
SLE: Arthritis
Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion
SLE: Serositis
a. Pleuritis—convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion Or
b. Pericarditis—documented by electrocardiogram or rub or evidence of pericardial effusion
SLE: Renal disorder
a. Persistent proteinuria— >0.5 g/day or greater than 3+ if quantitation not performed Or
b. Cellular casts—may be red cell, hemoglobin, granular, tubular, or mixed
SLE: Neurologic disorder
a. Seizures—in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, or electrolyte imbalance) Or
b. Psychosis—in the absence of offending drugs or known metabolic derangements (e.g., uremia, ketoacidosis, or electrolyte imbalance)
SLE: Hematologic disorder
a. Hemolytic anemia—with reticulocytosis Or
b. Leukopenia— <4,000 μL total on two or more occasions Or
c. Lymphopenia— <1,500/μL on two or more occasions Or
d. Thrombocytopenia— <100,000 μL in the absence of offending drugs
SLE: Immunologic disorder
a. Anti-DNA—antibody to native DNA in abnormal titer Or
b. Anti-Sm—presence of antibody to Sm nuclear antigen Or
c. Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of immunoglobulin G or immunoglobulin M anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test
SLE: Antinuclear antibody
An abnormal titer of antinuclear antibody by immunofluorescence of an equivalent assay at any point in time and in the absence of drugs known to be associated with “drug-induced lupus” syndrome
Confluent symmetric erythema and edema are centered over the malar eminences and bridges over the nose. The nasolabial folds are characteristically spared. The forehead, chin, and V area of the neck can be involved, and severe facial swelling may occur.
Localized Acute Cutaneous Lupus Erythematosus
Presents as a widespread morbilliform or exanthematous eruption often focused over the extensor aspects of the arms and hands and characteristically sparing the knuckles. Has been indiscriminately referred to as the maculopapular rash of SLE, photosensitive lupus dermatitis, and SLE rash.
Generalized Acute Cutaneous Lupus Erythematosus
Initially presents as erythematous macules and/or papules that evolve into hyperkeratotic papulosquamous or annular/polycyclic plaques. Characteristically photosensitive and occur in predominantly sun-exposed areas. Typically heal without scarring but can resolve with long-lasting, if not permanent, vitiligo-like leukoderma, and telangiectasias.
Subacute Cutaneous Lupus Erythematosus
Most common form of CCLE, which begin as red-purple macules, papules, or small plaques and rapidly develop a hyperkeratotic surface. Early lesions typically evolve into sharply demarcated, coin-shaped erythematous plaques covered by a prominent, adherent scale that extends into the orifices of dilated hair follicles. Typically expand with erythema and hyperpigmentation at the periphery, leaving hallmark atrophic central scarring, telangiectasia, and hypopigmentation.
Discoid Lupus Erythematosus
Rare variant of CCLE in which the hyperkeratosis normally found in classic DLE lesions is greatly exaggerated. The extensor aspects of the arms, the upper back, and the face are the areas most frequently affected.
Hypertrophic Discoid Lupus Erythematosus
Occurs in approximately 25% of patients with CCLE. The oral mucosa is most frequently affected; however, nasal, conjunctival, and genital mucosal surfaces can be targeted. In the mouth, the buccal mucosal surfaces are most commonly involved, with the palate, alveolar processes, and tongue being sites of less frequent involvement. Lesions begin as painless, erythematous patches that evolve to chronic plaques that can be confused with lichen planus.
Mucosal Discoid Lupus Erythematosus
Rare form of CCLE typified by inflammatory lesions in the lower dermis and subcutaneous tissue. Approximately 70% of patients with this type of CCLE also have typical DLE lesions, often overlying the panniculitis lesions.
Lupus Erythematosus profundus/Lupus Erythematosus panniculitis (Kaposi-Irgang disease)
Lesions initially develop as purple-red patches, papules, and plaques on the toes, fingers, and face, which are precipitated by cold, damp climates and are clinically and histologically similar to idiopathic chilblains (pernio). As they evolve, these lesions usually assume the appearance of scarred atrophic plaques with associated telangiectases. They may resemble old lesions of DLE or may mimic acral lesions of small vessel vasculitis. Associated with anti-Ro/ SS-A antibodies, and is linked to Raynaud’s phenomenon.
Chilblain Lupus Erythematosus
Variant of CCLE in which the dermal findings of DLE, namely, excessive mucin deposition and superficial perivascular and periadnexal inflammation, are found on histologic evaluation. This results in succulent, edematous, urticaria-like plaques with little surface change.
Lupus erythematosus tumidus
Antigens with High disease specificity for SLE
dsDNA (doubled-stranded DNA)
Sm
rRNP
PCNA (proliferating cell nuclear antigen)
Antigens with Low disease specificity for SLE
ssDNA (single-stranded DNA) Histones U1RNP Ro/SS-A La/SS-B Ku
First line treatment for Lupus Erythematosus-Specific Skin Disease
Topical glucocorticoids
Topical calcineurin inhibitor
Class I steroid qd–bid for 2 weeks alternating with pimecrolimus 1% or tacrolimus 0.1% bid for 2 weeks;
Intralesional triamcinolone acetonide 2.5–10.0 mg/cc
