Lupus Erythematosus and Variants



Lupus Erythematosus and Variants


Julie E. Jackson, MD

Chandra N. Smart, MD





Key Facts


Terminology



  • Multisystem autoimmune disorder with several variants that can affect skin alone or skin and multiple internal organs


Clinical Issues



  • SLE: Most common systemic features are fever, weight loss, fatigue, myalgias, and lymphadenopathy



    • Organ systems affected include skin, joints, kidneys, hematologic, pulmonary, and central nervous


  • ACLE: Cutaneous form most strongly associated with systemic disease, particularly lupus nephritis


  • SCLE: Papulosquamous or annular erythematous rash predominantly in sun-exposed areas


  • Chronic cutaneous lupus erythematosus



    • DLE, hypertrophic LE, LE/lichen planus overlap, tumid lupus erythematosus, chilblain LE, lupus panniculitis


    • Lesions seen in chronic cutaneous forms of LE typically leave dyspigmentation or scarring


Microscopic Pathology



  • DLE



    • Most forms of LE have histopathologic features similar to DLE, which is thought of as the prototypic example of cutaneous lupus erythematosus


    • Basal layer vacuolar interface change with basement membrane thickening


    • Superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate with increased dermal mucin deposition







Clinical photo shows acute cutaneous lupus with photodistributed erythema (as seen on the “V” of the chest).






Clinical photo shows DLE with typical facial erythematous dyspigmented atrophic scarred plaques image on the face and involving the conchal bowl image.


TERMINOLOGY


Abbreviations



  • Lupus erythematosus (LE)


Definitions



  • Multisystem autoimmune disorder with several variants that can affect skin alone or skin and multiple internal organs


ETIOLOGY/PATHOGENESIS


Autoimmunity



  • Proposed complex interaction between genetically susceptible patients with an environmental or infectious agent triggering or perpetuating the immune response


  • Numerous genes can affect overall autoimmunity, however much focus is on genes expressing major histocompatibility complex (MHC) class II



    • MHC class II is an important epitope that may recognize self antigens that cross-react with infectious agents in “molecular mimicry”


  • Certain human leukocyte antigen (HLA) types tend to be more strongly associated



    • HLA-B8, HLA-DR3, HLA-DR2, HLA-A1, HLA-B15, HLA-DRw6


CLINICAL ISSUES


Epidemiology



  • Gender



    • Predominantly affects young women (20s to 30s)



      • F:M = 6:1


      • Decreases to lower ratio in purely cutaneous forms of disease but maintains female predominance


  • Ethnicity



    • Affects African-American patients more often than Caucasians



      • Tends to have higher mortality and higher association with systemic symptoms in African-American patients


Presentation



  • Systemic lupus erythematosus (SLE)



    • Most common systemic features are fever, weight loss, fatigue, myalgias, and lymphadenopathy



      • Organ systems affected include skin, joints, kidneys, hematologic, pulmonary, and central nervous as included in criteria for classification


    • Any form of cutaneous lupus can be associated with systemic involvement


    • Nonspecific cutaneous findings include



      • Raynaud phenomenon, periungual dilated and tortuous capillary loops, livedo reticularis, urticaria, vasculitic lesions, non-scarring diffuse alopecia


  • Acute cutaneous lupus erythematosus (ACLE)



    • Cutaneous form most strongly associated with systemic disease, particularly lupus nephritis with anti-dsDNA antibodies


    • Localized or generalized erythema with photosensitivity and malar rash


  • Subacute cutaneous lupus erythematosus (SCLE)



    • Papulosquamous or annular erythematous rash predominantly in sun-exposed areas that results in dyspigmentation but not typically scarring


    • Strongly associated with anti-Ro antibody


    • Neonatal lupus



      • Form of SCLE in neonates born to mothers with anti-Ro antibodies; typically presents as papulosquamous annular rash periorbitally and photodistributed


      • Neonates are also at risk for congenital heart block, hepatobiliary disease, and thrombocytopenia


  • Chronic cutaneous lupus erythematosus




    • Discoid lupus erythematosus (DLE)



      • Scarred, atrophic, dyspigmented plaques with follicular plugging seen typically on face, scalp, and conchal bowl


      • Heal with scarring, dyspigmentation, and even alopecia if scalp involvement is present


      • One of most common cutaneous forms of lupus with only 5-10% of patients progressing to systemic lupus erythematosus


      • Tends to be higher risk for progression in patients with disseminated discoid lesions


    • Hypertrophic lupus erythematosus



      • Variant of DLE with overlying thick hyperkeratotic scaling


    • LE/lichen planus overlap



      • Syndrome with clinical and histologic features of both lichen planus and lupus erythematosus that can be difficult to distinguish from lichenoid drug eruption


      • Can occur in lupus erythematosus patients on antimalarials


    • Tumid lupus erythematosus



      • Cutaneous form of LE with low incidence of SLE occurring as edematous plaque typically on face without overlying epidermal surface change


    • Chilblain lupus erythematosus



      • Acrally distributed dusky or purple plaques that appear or worsen in moist, cold climates


    • Lupus panniculitis (profundus)



      • Depressed, intensely scarred plaques typically on upper extremities or upper trunk occurring from involvement of panniculus


      • If overlying lesions of DLE are present, disease is referred to as lupus profundus


  • Bullous lupus



    • Bulla or vesicles appearing in patients with LE due to intense inflammation; can be seen in patients with ACLE, SCLE, or, rarely, DLE


  • Rowell syndrome



    • Lesions seen in acute cutaneous lupus with erythema multiforme-like lesions


  • Drug-induced LE



    • Hydralazine, procainamide, minocycline, sulfonamides, penicillin, anti-convulsants, griseofulvin (SCLE), terbinafine (SCLE), hydrochlorothiazide (SCLE), and penicillamine (unmasks true SLE)


Laboratory Tests



  • Serologies



    • ANA (95% positive in SLE), anti-double-stranded DNA (dsDNA), anti-Smith antibody (anti-Sm), antinuclear ribonucleic acid protein (rRNP), anti-La antibody


    • Anti-Ro antibody, anti-single-stranded DNA antibody (ssDNA), antiphospholipid antibodies (anticardiolipin antibody and lupus anticoagulant)


  • Systemic involvement



    • CBC with differential to check for anemia, thrombocytopenia, leukopenia, or lymphopenia


    • Serum creatinine and urinalysis for renal involvement


  • Other tests



    • Low serum complement, false-positive syphilis serologies, elevated ESR, or positive rheumatoid factor


Prognosis



  • Variable prognosis depending on type of LE and extent of systemic involvement, ranging from purely cutaneous disease to severe systemic disease with effect on overall morbidity and mortality


1997 Update of 1982 American College of Rheumatology Revised Criteria for Classification of SLE



  • For diagnosing patients in clinical studies, 4 of the following 11 criteria must be met simultaneously or serially during any time period



    • Malar rash


    • Discoid rash


    • Photosensitivity


    • Oral ulcers



    • Nonerosive arthritis: Involving 2 or more peripheral joints


    • Pleuritis or pericarditis


    • Renal disorder: Proteinuria > 0.5 g/day or cellular casts


    • Neurologic disorder: Seizures or psychosis


    • Hematologic disorder: Hemolytic anemia or leukopenia or lymphocytopenia or thrombocytopenia


    • Immunologic disorder: Positive anti DNA antibody or anti Smith antibody or antiphospholipid antibodies (anticardiolipin antibodies), lupus anticoagulant antibodies, false-positive syphilis serologic test


    • ANA: An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in the absence of drugs known to induce ANAs


MICROSCOPIC PATHOLOGY


Histologic Features



  • DLE



    • Hyperkeratosis with follicular dilation and keratin plugging often overlying thinned or atrophic epidermis with loss of rete ridge pattern


    • Basal layer vacuolar interface change over broad front with associated thickening of basement membrane that can be highlighted by periodic acid-Schiff (PAS) staining


    • Dermal pigmentary incontinence with dermal edema and telangiectatic vessels


    • Superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate


    • Increased dermal mucin appreciated by increased clear spaces between dermal collagen bundles or spaces filled with amorphous blue material composed of hyaluronic acid



      • Highlighted by staining with Alcian blue or colloidal iron


    • Late changes include fibrosis of dermis and loss of pilosebaceous follicular units


  • SLE



    • Early lesion of malar erythema shows basal layer vacuolar change, dermal edema, and superficial and deep lymphohistiocytic infiltrate


    • Histology can be indistinguishable from that of SCLE and commonly DLE


    • Compared to DLE, thickening of basement membrane may be less with SLE


  • SCLE



    • Features classic for DLE are seen in SCLE but with more marked epidermal atrophy, less conspicuous basement membrane thickening, and less follicular plugging


  • Hypertrophic LE



    • Changes as seen in DLE with marked hyperkeratosis, hypergranulosis, and acanthosis


  • LE/lichen planus overlap



    • Histopathologic changes of both conditions are evident on biopsy


    • Features of lichen planus include overlying compact hyperkeratosis with wedge-shaped hypergranulosis, acanthosis, and dense lichenoid lymphocytic infiltrate leading to obscuring of dermal-epidermal junction (DEJ)



      • Basal layer vacuolar change with epidermal Civatte and dermal colloid bodies are also seen


    • Features of LE include basal layer vacuolar interface change with superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate with increased dermal mucin


  • Tumid LE

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lupus Erythematosus and Variants

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