CASE REPORT Canine Pemphigus Vulgaris Treated with Salt Therapy

G.P. OLYNYK AND B.J. GUTHRIE Edgemont Veterinary Clinic, #12, 34 Edgedale Drive North West, Calgary, Alberta T3A 2R4

Summary treated with antibiotics, prednisone, euthanasia, gold salt therapy, or A nine year old spayed female Collie vitamins and metronidazole with no further antibiotic-corticosteroid treat- was diagnosed as having pemphigus lasting or dramatic improvement. The ments with the owner. vulgaris. Response to corticosteroid dog had previously been diagnosed as On May 13, 1982 we initiated auro- and antibiotic therapies was unsatis- having hip dysplasia and secondary thioglucose3 therapy as outlined pre- factory. Aurothioglucose therapy was arthritis. viously (1). Two intramuscular injec- used later as the sole treatment. The tions of 5.0 and 10.0 mg were given as dog achieved a complete remission Clinical Findings and Treatment tests of tolerance on May 13 and 20 lasting at least ten months. At first presentation, the physical respectively. The therapeutic series examination was unremarkable with involved six weekly intramuscular Resumme' the exception of skin lesions. The injections at 1.0 mg/kg. These injec- Traitement du pemphigus vulgaire refractory nature and the location and tions were given May 27, June 3, 10, canin avec de l'aurothioglucose nature of the lesions suggested a diag- 17, 24 and 30. No other therapy was Les auteurs ont diagnostique la nosis of pemphigus vulgaris. used. A physical examination, weigh- pemphigus vulgaire, chez une chienne A biopsy was obtained; the resulting in and discussion with the owner Collie castree et agee de neuf ans. Un histopathology suggested an immune accompanied each injection. Side traitement a base de corticosteroides et etiology. Prednisone' orally at 15 mg effects were not observed in associa- d'antibiotiques se revela inadequat. Ils every eight hours for 14 days was tion with this therapy. Improvement deciderent ulterieurement de n'utiliser initiated. The response was favorable, was noted at the June 17 visit; this que de l'aurothioglucose et la chienne but the dog deteriorated rapidly as the improvement continued steadily. mit au moins dix mois a guerir. dose was reduced. Through January Further injections at 1.0 mg/kg were and February of 1982, the dog's prob- given July 30, August 18, September 9, Introduction lem worsened with raw scaling crusts October 8, November 8 and December Attempts have been made to achieve developing on the lips, chin, eyelids, 9, 1982. The vast majority of skin remission or at least control autoim- bridge of nose, anus and vulva despite lesions had resolved by September and mune skin disorders with a variety of high doses of corticosteriod. Treat- the dog was essentially lesion-free with drugs. Many of these substances as ment with trimethoprim 4802 every 12 hair regrowth by December. The sole therapies or in combinations hours for ten days to control a sus- patient has remained in good health either lack efficacy and/or may cause pected secondary bacterial involve- with the exception of its arthritic hips undesirable side effects. Encouraging ment proved unrewarding. All medi- up to the time of this writing (October reports concerning gold salt therapy in cations were discontinued March 18, 1983). veterinary medicine are beginning to 1982 and a more thorough laboratory appear but clinical experience is still workup was performed March 23, Discussion somewhat limited. This report records 1982. All laboratory data are summar- Pemphigus vulgaris is an immune- one such experience. ized in Table 1. A diagnosis of pemphi- mediated bullous skin disorder in gus vulgaris was confirmed by direct which autoantibodies against intracell- History tissue immunofluorescence. ular cement substances are believed to On November 3, 1981 a 20 kg nine By the time the immunofluores- reduce the cohesiveness of epidermal year old spayed female Collie was cence test had returned, the patient's cells to one another and to the dermis. presented with salivary drooling and condition had deteriorated further, to As a result, clefts form in the epidermis crusting raw lesions of the lip margins. include the pad margins, nail beds and which coalesce and enlarge to form the The problem had begun approxi- patches of skin on the metacarpus and characteristic flaccid bullae (2). Clini- mately one month earlier and had been metatarsus. We discussed options of cally, pemphigus vulgaris most often

'Deltasone 5 mg, TUCO Products Co., Orangeville, Ontario. 2Tribrissen 480, Burroughs Wellcome Inc., Kirkland, Quebec. 3Solganol, Schering Corporation, P.O. Box 500, Kenilworth, New Jersey 07033.

168 Can Vet J 1984; 25: 168-170. TABLE I weekly injections a plateau in serum SUMMARY OF CLINICAL PATHOIOGY RESULTS PRECEDING AND FOLLOWING AUROTHIOGLUCOSE gold concentrations is not reached for several weeks. This may explain the Parameter Normal value March 23, 1982 April 7, 1982 July 30, 1982 delayed therapeutic response. In indi- PCV 37-55% 40 viduals treated with , rela- Platelets adequate adequate tively high levels are found in the reti- RBC regeneration adequate adequate Metarubricytes 2/ 100 WBC culoendothelial system, and rather low WBC /mm3 6000-17000 9150 levels are detected in the epidermis and Neutrophils , mm3 3600-11500 7200 adnexa. This would suggest that the Band cells /mm3 0-300 100 site of action of gold salts would be Lymphocytes / mm3 1000-4800 650 Monocytes /mm3 150-1350 1100 more likely on the immune process, Eosinophils /mm3 100-1250 200 rather than protection of target tissues Skin scraping neg (20). Fecal exam neg Toxic side effects of gold com- mg,/ dL 65-130 86 74 109 pounds, including dermatitis, stomati- BUN mg/dL 10-30 12 10 29 Creatinine mg/dL 1-2.0 0.7 0.6 1.0 tis, allergic reactions, nephrotic syn- Na mEq/'L 140-155 154 153 145 drome and other signs, have been K mEq/L 4.0-5.7 4.0 5.4 4.1 reported in human medicine, but Ca mg/dL 8.5-11.5 9.6 10.3 10.9 experience with canine patients is still P mg/dL 3.0-7.0 3.7 5.2 3.7 the TP g/dL 5.4-7.5 5.2 7.0 6.9 somewhat limited (1,15). Among Albumin g/dL 2.3-4.0 2.6 3.9 3.3 reported side effects in dogs, are Globulin g/dL 2.7-4.4 2.6 3.1 3.6 thrombocytopenia and hemorrhage Total bili mg/dL 0-1.0 0 0 0.1 (14). When side effects occur, they are Alk phos l.U.I/L 12-84 724 164 96 most often mild and occur soon after SGPTI.U./L 9-63 267 162 28 Histopathology: acantholysis, cleft formation, possibly immune-mediated initiation of therapy (21). Reactions Direct immunofluorescence: strong IgG fluorescence without much C3 depostion are most commonly treated by stop- USG- urinalysis 1.026 ping the gold injections and instituting pH 7.0 corticosteroid, and/or D Protein mg/dL 30 Most salt Glucose g/dL 0 (22). gold Ketones mg/dL 0 treatment protocols recommend test Bilirubin 0 injections with gradually increasing Blood 0 dosages to detect variations in patient Urobilinogen Ehrlich tolerance (1). It would appear from U/dL 0 early reports that many individuals are more successfully managed with gold salts than with other therapies, and presents as patches ofcrusting, oozing, appear to have several physiological may be more likely to achieve total and scaling, alopecia and erythema, pre- effects, but the exact mechanism by sustained remissions (1,15). Unfortu- dominantly, but not exclusively affect- which beneficial results are often nately, the expected duration ofremis- ing mucocutaneous junctions. Pruritis obtained is still an area of active sion achieved by the use of aurothio- ranges from very mild to severe (3,4). research. Some of these effects include glucose is as yet unknown. Diagnosis is suspected on the basis of decreases in the following: lympho- Elevations of liver enzymes are history, clinical signs, and histopa- cytic proliferation (15) immunoglo- known to occur with corticosteroid thology, but is confirmed by direct bulin production (16), epidermal therapy and may also be seen with the tissue immunofluorescence (5). Un- enzyme activity (17), prostaglandin use of sulfa drugs such as trimetho- treated, the course is most often synthesis (17) and phagocytic ability prim. We believe that the elevated chronic and unremitting, sometimes (12). Gold salts also appear to enhance alkaline phosphatase and transami- fatal. The natural remission rate is collagen stability and inactivate com- nase seen in this patient are due to unknown. Factors controlling the plement proteins (18). these drugs inasmuch as the values onset and regression ofthese disorders There is little published research returned toward normal after these are poorly understood (5). regarding of gold drugs were withdrawn. The control of autoimmune skin compounds in the canine (1,15). In Since the naturally occurring remis- disorders has been attempted using humans, a single injection ofgold salts sion rate of pemphigus vulgaris is many drugs, including corticosteroids, is followed by a decline in blood con- unknown, we do not see the recovery (1,6), (7,8), dap- centrations by first order kinetics (19). after aurothioglucose therapy as proof sone (9), (10), azothio- Although the serum half-life of gold of a cause and effect relationship. prine (I1), combination therapies (12) salts following a single injection These diseases are difficult to study and more recently, gold salts (1). appears to be quite short, gold salts are because of their unpredictable nature, Many of these treatments either lack sequestered in various tissues and infrequent occurrence and the inabil- efficacy and/or induce undesirable excreted from the body very slowly, ity to produce the condition experi- side effects (1,13,14,15). Gold salts primarily by the renal route (20). With mentally. More research and expe-

169 rience with gold salt therapy will be 7. McKELVEY EM, HASEQAWA J. Cyclophos- 15. SCOTT DW, MANNING TO. SMITH DA, LEWIS RM. needed to ascertain its true value in the phamide and pemphigus vulgaris. Arch Observations on the immunopathology and treatment of this condition. Dermatol 1971; 103: 198-200. therapy of canine pemphigus and pemphi- 8. KRAIN LS, LANDAU JW, NEWCOMER VD. Cyclo- goid. J Am Vet Med Assoc 1982; 180:48-52. phosphamide in the treatment ofpemphigus 16. LORBER A. SIMON T, LEEB J, PETER A, et al. References vulgaris and bullous pemphigoid. Arch Chrysotherapy - suppression of immuno- 1. MANNING TO, SCOTT DW, KRUTH SA, SOZANSKI Dermatol 1972; 106: 657-661. globulin synthesis. Arthritis Rheum 1978; M, LEWIS RM. Three cases of canine pemphi- 9. PIAMPHONGSANT T. Pemphigus controlled 21: 785-791. gus foliaceus, and observations on chryso- by dapsone. Br J Dermatol 1976; 94: 17. PENNYS NS. ZIBOH V. GOTTLIEB NL, KATZ S. therapy. J Am Anim Hosp Assoc 1980; 16: 681-686. Inhibition of prostaglandin synthesis and 189-202. 10. LEVER WF, GOLDERBER HS. Treatment of human epidermal enzymes by aurothiomal- 2. FUKUSHIMA K. Pathogenesis of pemphigus pemphigus vulgaris with methotrexate. ate in vitro: Possible actions of gold in pem- vulgaris in dog and man - A review. Can Arch Dermatol 1969; 100: 70-78. phigus. J Invest Derm 1974; 63: 356-361. Vet J 1982; 23: 135-137. II. ROENIGK HH, DEODHAR S. Pemphigus treat- 18. PERSELLIN RH, HESS EV. ZIFF M. Effect of a 3. HURVITZ Al. FELDMAN E. A disease in dogs ment with . Arch Dermatol gold salt on the immune response. Arthritis resembling human pemphigus vulgaris: 1973; 107: 353-357. Rheum 1977; 110: 99-106. Case reports. J Am Vet Med Assoc 1975; 12. VERNON-ROBERTS B, JESSOP JD, DORE J. 19. GERBER RC, PANLUS HE. Gold therapy. Clin 166: 585-590. Effects of gold salts and on Rheum Dis 1975; 1: 307-318. 4. HOSKINS, JD, OUVERSON A, SCHLATER L, inflammatory cells (II). Suppression of 20. GOTTLIEB NL, SMITH PM, SMITH EM. Gold PROCTOR SE. Pemphigus vulgaris in a dog: A inflammation and phagocytosis in the rat. excretion correlated with clinical course case report. J. Am Anim Hosp Assoc 1977; Ann Rheum Dis 1973; 32: 301-307. during chrysotherapy in rheumatoid arthri- 13: 161-167. 13. CROW SE. THEILEN GH. MADEWELL BR. tis. Arthritis Rheum 1972; 15: 582-592. 5. SCOTT DW. Immunologic skin disorders in WELLER RE. HENNESS AM. Cyclophospham- 21. PENNYS NS, EAGLSTEIN WH, INDIGEN S, FROST the dog and cat. Vet Clin North Am 1978; 8: ide induced cystitis in the dog and cat. J Am P. Gold sodium thiomalate in the treatment 641-664. Vet Med Assoc 1977; 171: 259-262. of pemphigus. Arch Dermatol 1973; 108: 6. ROSENBERG FR, SANDERS S, NELSON DT. Pem- 14. FADOK VA, JANNEY EH. Thrombocytopenia 56-60. phigus. A 20-year review of 107 patients and hemorrhage associated with gold salt 22. PRODUCT INFORMATION SHEET. Solganol. treated with corticosteroids. Arch Dermatol therapy for bullous pemphigoid in a dog. J Kenilworth, New Jersey: Schering Corp, 1976; 112: 962-970. Am Vet Med Assoc 1982; 181: 261-262. 1980.

BOOK REVIEW

Current Techniques in Small organs or disease conditions. disagreement with some of the Animal Surgery. Edited by M. A number of new sections have been recommendations given. As the edi- Joseph Bojrab. Published by Lea & added, including ones on burns, tors state though, this does not detract Febiger, Philadelphia, Pennsylva- trauma, electrosurgery technique and from the book's value, and a short ref- nia. 1983. 8 11 pages. Price $106.25. suture materials. In addition, many of erence list after each chapter provides the contributors are new, and while a means for the reader to make his own It is eight years since the first edition some chapters, such as the one on pha- assessments. of this book was published. A second ryngostomy tube use, remain un- As with the first edition, the text- edition has now appeared, intended to changed from the first edition, most book is not, nor does it claim to be, provide an updated collection of sur- are considerably altered. The result is encyclopedic. One new section on gical procedures for the practicing an increase in size by more than two surgical techniques for exotic species veterinarian. hundred pages. There are also three contains only two mammalian chap- The textbook has the same organi- hundred new illustrations, mainly ters, one on feline onychectomy, the zation as the previous edition: two clear and accurate line drawings. other on anal sac removal in ferrets. main parts on soft tissue and ortho- Many familiar names from the The remaining chapters are devoted to pedic procedures, each with its own American College of Veterinary Sur- avian surgery. consulting editor. Each part is subdi- geons appear amongst the 129 con- While the practitioner will thus vided into sections on major body sys- tributors, and because each article require a more basic textbook as an tems, and these are divided in turn into represents an opinion on an often con- adjunct, this new edition will still chapters dealing with individual troversial topic, there will naturally be prove an invaluable addition to his library. J. Cockshutt.

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