Cutaneous Lupus Erythematosus 2008: Presentation & Management
ACVIM 2008
Danny W. Scott, DVM, DACVD
Ithaca, NY, USA

There are currently at least four forms of lupus erythematosus (LE) in dogs. Systemic lupus erythematosus (SLE) is the most severe form because it is a multisystemic disease wherein about 50% of the patients have skin disease.1,2 This presentation will focus on the remaining forms of LE which are predominantly skin diseases.

Pathogenesis

The etiopathogenesis of the skin lesions in any form of LE is incompletely understood.2 Genetic associations have been made in dogs,2 and suggested precipitating factors include viral infections, drugs (to include vaccines), hormones, chemical exposure, and (in humans) cigarette smoking.2

A current hypothesis for the pathogenesis of skin lesions in genetically susceptible individuals is as follows:2

1.  Ultraviolet light (both UVB and UVA) penetrating to the level of epidermal basal cells induces, on the keratinocyte surface, the enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and of autoantigens (e.g., Ro) previously found only in the nucleus or cytoplasm.

2.  Specific autoantibodies to these antigens, that are present in plasma and in tissue, fluids, attached to keratinocytes and induce antibody-dependent cytotoxicity of keratinocytes.

3.  Injured keratinocytes release interleukin-2 (IL-2) and other lymphocyte chemoattractants, resulting in a lymphohistiocytic infiltrate. Inappropriate activation of keratinocyte apoptosis occurs.

Discoid Lupus Erythematosus (DLE)

Canine DLE was first documented in 1979,3 and reviewed in 1983,4 and 1987.5 It is the most common form of cutaneous LE, and accounted for 0.27% of the dogs with skin diseases examined at a university clinic.5 There is probably no strong sex predilection, and no age predisposition has been reported. Collies, Shetland sheepdogs, German shepherd dogs, Siberian huskys, and Brittany spaniels appear to be over-represented.2

Clinical signs initially include depigmentation, erythema, and scaling of the nasal planum. A common early change is the loss of the normally rough, cobblestone-like architecture of the nasal planum. Later lesions include erosion, ulceration, and crusting. With time, lesions may progress proximally up the bridge of the nose. Less commonly, lesions may occur periorbitally, on the pinnae, on the lips, on the distal limbs, and on the genitals. Small punctate ulcers may be detected in the oral cavity, especially the tongue or palate. Rarely, dogs may present only with lesions of the pinnae2,6 or with nasodigital hyperkeratosis.2,4 Pruritus and pain are variable. Scarring and variable degrees of permanent leukoderma may occur. Rarely, deeply ulcerated nasal lesions damage arterioles, resulting in episodic, pulsatile hemorrhage. DLE is not a systemic disease, and affected dogs are otherwise healthy.

DLE is commonly exacerbated or precipitated by exposure to ultraviolet light. Thus, the disease often is more severe in the summer and in sunny climates. Chronic, uncontrolled DLE has rarely been reported to undergo malignant transformation into squamous cell carcinoma of the nasal planum.7

Diagnosis is based on history, physical examination, and biopsy.2 Immunofluorescence and immunohistochemical testing demonstrate immunoglobulin and complement at the basement membrane zone.2 However, false-positive and false-negative results are common.2 Results of routine laboratory determinations (hemogram, biochemistry, urinalysis) and antinuclear antibody tests are usually within normal limits.2 Dermatohistopathological findings include interface dermatitis (hydropic, lichenoid, or both).2,8 Dermal mucinosis and focal thickening of the basement membrane zone are common findings.2,8

The prognosis for DLE is good.2 Therapy of DLE must be appropriate to the individual.2 Mild cases may be controlled by, and all cases benefit from, avoidance of exposure to intense sunlight (from 8 AM to 5 PM), the use of topical sunscreens (SPF >30), and the use of topical glucocorticoids (e.g., betamethasone ointment, fluocinolone/DMSO solution [Synotic®]).2 Commonly used therapeutic agents include:2,4 (a) prednisolone or methylprednisolone (2 mg/kg/day initially);2,4 (b) tetracycline and niacinamide (250 to 500 mg of each q8h initially);2,9 (c) vitamin E (400 to 800 IU q12h);2,4 (d) omega-6/omega-3 fatty acids (e.g., Eukanuba® dog foods);2 and (e) tacrolimus 0.1% (Protopic®) q12h.10

Vesicular Cutaneous Lupus Erythematosus (VCLE)

Canine VCLE was first described as "idiopathic ulcerative dermatosis of collies and Shetland sheepdogs" in 1995.11 It was dubbed a homologue of subacute cutaneous LE of humans in 2004.12 To date, it has been reported in collies, Shetland sheepdogs, and a Japanese spitz.13 Females are over-represented (2.4:1), and affected dogs have ranged from 3 to 11 years old.12

Clinical signs usually occur or are exacerbated in the summer. Annular-to-polycyclic-to-serpiginous ulcers and epidermal collarettes occur on sparsely-haired areas of skin (especially ventral abdomen, axillae, groin, and pinnae). The oral mucosa and mucocutaneous junctions may be involved. Pruritus and pain are variable. Affected dogs are usually otherwise healthy.

Diagnosis is based on history, physical examination, and biopsy.12 Immunofluorescence and immunohistochemical testing demonstrate immunoglobulin and complement at the basement membrane zone.12 However, false-positive and false-negative results are common.2 Results of routine laboratory determinations (hemogram, biochemistry, urinalysis) are usually within normal limits. Routine antinuclear antibody tests are negative, but antibodies to extractable nuclear antigens (Ro/SSA or La/SSB) are positive in over 80% of the dogs.12 Dermatohistopathological findings include a cell-rich interface dermatitis with frequent intrabasilar cleft and vesicle formation.8,12

The prognosis for VCLE is guarded.14 Photoavoidance and photoprotection are very important. Information on therapy is limited:14 (a) prednisolone alone (1 dog); (b) prednisolone and doxycycline (1 dog); (c) prednisolone and azathioprine (3 dogs); (d) pentoxifylline (4 dogs) no response; (e) tetracycline and niacinamide (1 dog) no response; and (f) cyclosporine (1 dog).15

Exfoliative Cutaneous Lupus Erythematosus (ECLE)

Canine ECLE was first described as "hereditary lupoid dermatosis of German shorthaired pointers" in 1995.16 To date, it has been reported in German shorthaired pointers. Females are over-represented (2:1), and affected dogs range from 2 months to 4 years of age.17-19 Pedigree analysis suggests an autosomal recessive inheritance.19

Scaling, hair casts, and hair loss usually begin on the head, pinnae, and muzzle, and progress to the dorsal trunk, limbs, and ventral trunk. Crusts and ulcers may occur in 24% of the dogs. Depigmentation and ulceration are occasionally seen on the nasal planum. Pruritus is usually mild or absent. Peripheral lymphadenopathy is detected 32% of the dogs.19 Episodic pain (back arching, vocalization, difficulty rising/sitting) and intermittent fever may be seen in about 12% of the dogs.19

Diagnosis is based on history, physical examination, and biopsy.19 Immunofluorescence and immunohistochemical testing demonstrate immunoglobulin at the basement membrane zone of the epidermis (100%) and hair follicles (41%).19 Circulating IgG autoantibodies that target hair follicle and sebaceous gland are detected in 57% of the cases.19 This testing is not available to practitioners. Results of routine laboratory examinations (hemogram, biochemistry, urinalysis) and antinuclear antibody testing are within normal limits.19 Dermatohistopathological findings include a cell-rich interface dermatitis and mural folliculitis, with sebaceous glands being absent in 50% of the specimens.19

The prognosis for ECLE is guarded.18,19 Response to treatment is unpredictable and, when initially achieved, is often not sustained.18,19 In addition, the disease may wax and wane, making short-term responses to therapy difficult to interpret. Individual dogs have responded to tetracycline and niacinamide and/or omega-6/omega-3 fatty acids.18,19 Other dogs have failed to respond to these as well as prednisolone (1 to 2 mg/kg/day), azathioprine, vitamin E, vitamin A, etretinate, leflunomide, and cyclosporine.18,19 Many dogs were euthanized due to poor response, side effects, financial burden, and demodicosis.19

Other Poorly Characterized Forms of Cutaneous LE

Widespread "DLE" has been reported in two dogs.20,21 The dogs had erythema, scaling, and alopecia involving the face, trunk, and limbs. The dogs were otherwise healthy, routine laboratory examinations and antinuclear antibody testing were within normal limits, and skin biopsy findings were consistent with DLE. One dog responded to methylprednisolone and azathioprine, the other to prednisolone.

Perianal (and perivulvar?) LE has been reported in 9 dogs.22,23 The dogs had dyschezia and frequent hematochezia and constipation. Perianal lesions included depigmentation, erosions, and ulcers. Skin biopsy findings were consistent with DLE. Two dogs were treated with prednisolone (2 mg/kg/day), achieved remission, and remained in remission after therapy was stopped.22 Four dogs responded to prednisolone and azathioprine, but required alternate-day prednisolone or azathioprine.22 One dog was controlled with tetracycline and niacinamide.22

References

1.  Scott, et al. J Am Anim Hosp Assoc 1983;19:461.

2.  Scott DW, et al. Muller & Kirk's Small Animal Dermatology VI 2001:701.

3.  Griffin CE, et al. Vet Immunol Immunopathol 1979;1:79.

4.  Scott DW, et al. J Am Anim Hosp Assoc 1983;19:481.

5.  Scott DW, et al. Compend Cont Edu 1987;9:539.

6.  Scott DW, et al. J Am Anim Hosp Assoc 1984;20:579.

7.  Scott DW, et al. Vet Dermatol 1995;6:99.

8.  Crowson AN, et al. J Cutan Pathol 2001;28:1.

9.  White SD, et al. J Am Vet Med Assoc 1992;200:1497.

10. Griffies JD, et al. J Am Anim Hosp Assoc 2004;40:29.

11. Ihrke PJ, et al. Kirk's Current Veterinary Therapy XII 1995:649.

12. Jackson HA, et al. Vet Dermatol 2004;15:230.

13. Yamamura C, et al. Jpn J Vet Dermatol 2005;11:125.

14. Jackson HA. Vet Dermatol 2004;15:37.

15. Font A, et al. Vet Dermatol 2006;17:440.

16. Gross TL, et al. Veterinary Dermatopathology: A Macroscopic and Microscopic Evaluation of Canine and Feline Skin Diseases 1992:26.

17. White SD, et al. Kirk's Current Veterinary Therapy XII 1995:605.

18. Vroom MN, et al. Vet Dermatol 1995;6:93.

19. Bryden SL, et al. Vet Dermatol 2005;16:239.

20. Murayama N, et al. Jpn J Vet Dermatol 2006;12:87.

21. Nagata M, et al. Jpn J Vet Dermatol 2004;10:119.

22. Schrauwen E, et al. Vet Rec 2004;154:752.

23. Gerhauser I, et al. Vet Pathol 2006;43:761.

Speaker Information
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Danny Scott, DVM, DACVD
Cornell University
Ithaca, NY


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