Volume 22Number 6, Part 1June 1990

4. Birt AR, Davis RA. Photodermatitis in North AmericanIndians: familial actinic prurigo. Int J Dermatol1971;10:107-14.

5. Brandt R. Dermatologicalobservationson the Navaho res­ervation.Arch Dermatol 1958;77:581-5.

6. Hojyo-Tomoka MT, Dominquez-SotoL. Clinical and ep­idemiological characteristics of polymorphous light erup­tion in Mexico. Castellania 1975;3:21-3.

7. Cordero CFA. Sindrome cutaneoguatemalense en la der­matitisactinica. Med Cutan Ibero Lat Am 1976;4:393-400.

8. AokiT, Fujuta M. Actinic prurigo: a case report with suc­cessful induction of skin lesions. Clin Exp Dermatol1980;5:47-52.

HLA in actinicprurigo

9. AddoHA, Frain-Bell W. Actinic prurigo:a specific photo­dermatosis. Photodermatology 1984;1:119-28.

10. Calnan CD, Meara RH. Actinic prurigo (Hutchinson'ssummer prurigo). Clin Exp Dermatol 1977;2:365-72.

11. Epstein JH. Polymorphous light eruption. J AM ACADDERMATOL 1980;3:329-43.

12. Lane PR, Harms VL, Hogan DJ. Patch testing in actinicprurigo. Contact Dermatitis. 1989;21:249-54.

13. KostyuDD, Amos DB. Mysteries of the Amerindians.Tis­sue Antigens 1981;16:111-23.

14. Bernal JE, Duran de Rueda MM, de Brigard D. Humanlymphocyte antigen in actinic prurigo. J AMACAD DER­MATOL 1988;18:310-2.

Subcorneal pustular dermatosis in dogs and inhuman beings: Comparative aspectsKathleen M. Kalaher, DVM, and Danny W. Scott, DVM Ithaca, New York

Subcorneal pustular dermatosis is a rare disorder in dogs and in human beings. A retrospec­tive study of 13 cases of canine subcorneal pustular dermatosis indicates that many of theclinicopathologic features of this disease are similar in both species. In both the condition ischaracterized by a variably pruritic, sterile, pustular eruption that is resistant to antibioticsand glucocorticoids. The therapeutic response to dapsone is not uniformly successful in eitherspecies, and the disorder tends to be chronic and recurrent. (J AM ACAD DERMATOL1990;22:1023-8.)

Subcorneal pustular dermatosis (Sneddon­Wilkinsondisease) is a rare, idiopathic disorder thatwas originally described in 1956.1 Subcorneal pus­tular dermatosis was first reported in the dog in1977.2, 3 To date, only 33 cases have been describedin the veterinary literature.i" The purpose of thisarticle is (1) to present the results of a retrospectivestudy of 13 cases of canine subcorneal pustular der­matosis and (2) to summarize the comparativeaspects of this condition in dogs and in humanbeings.

CANINE SUBCORNEAL PUSTULARDERMATOSIS

From 1977 to 1988 subcorneal pustular derma­tosis was diagnosed in 13 dogs at the New York

From the Department of Clinical Sciences, New York State College ofVeterinary Medicine, Cornell University.

Accepted for publication Sept. 2, 1989.

Reprint requests: Danny W. Scott, DVM, Department of Clinical Sci­ences, New York State College of Veterinary Medicine, CornellUniversity, Ithaca, NY 14853.

16/1/16605

State College of Veterinary Medicine (Table I).The dogs ranged in age from 1 to 12 years, withan average age of 6.3 years. Eight dogs were fe­males (four spayed and four intact), and five weremales (all intact). As has been reported pre­viously.v" there was a breed predilection for theminiature schnauzer. Of the 13 dogs, 6 (46%) wereminiature schnauzers whereas this breed account­ed for only 1.3%of the general canine hospital pop­ulation.

The duration of clinical signs before presentationvaried from 2 months to 3 years. In 11 dogs the der­matosis was generalized at the time of presentation.Information regarding the initial site(s) of involve­ment was available for nine of these dogs. The earlydistribution oflesions was variable and included thetrunk (three cases), the trunk and extremities (two),the trunk and ears (one), the extremities (one), andthe head and extremities (one). Lesions were re­ported to be generalized from the onset in one dog.In the two dogs with localized disease, lesions werenoted on the head, groin, and extremities in one caseand on the trunk and ears in one case. Although the

1023

1024 Ka/aher and Scott

Fig. 1. Multiple nonfollicularpustuleson abdomenandmedial aspect of thighs of dog.

Fig. 2. Close-up view of nonfollicular pustules.

pruritus varied from nonexistent to severe, most dogswere mildly to moderately pruritic. A peripherallymphadenopathy was noted in three cases. Py­rexia, partial anorexia, and depression, in conjunc­tion with the dermatosis, were noted in one dog (case11). Systemic signs were observed in three otherdogs but did not correlate with the onset of the skineruption. Iatrogenic Cushing's disease was presentin two dogs (cases 5 and 12). The third dog (case 7)had a 3-week history of a progressive neurologic dis­order of unknown cause.

Primary skin lesions consisted of nonfollicularpustules, often green-yellow in hue and more or lesssymmetric in distribution (Figs. 1 and 2). Secondaryskin lesions included epidermal collarettes, erosions,scales, and crusts. The lesions tended to heal cen­trally, often with hyperpigmentation, and to spreadperipherally, resulting in annular and serpiginousconfigurations (Fig. 3).

Journal of theAmerican Academy of

Dermatology

Fig. 3. Pustules, epidermal collarettes, and scales ontrunk of dog. Note annular configuration with centralhealing and hyperpigmentation.

Skin scrapings and fungal cultures were negativein all 13 dogs. Bacterial cultures were negative inseven cases. In the five dogs with positive culturescoagulase-negative (three cases) and coagulase­positive (two) staphylococci were isolated. Cytologicexamination of lesions was performed in nine casesand revealed numerous nondegenerate neutrophils,occasional acanthocytes, and no microorganisms.

Hemograms were checked in all cases and re­vealed mild to moderate mature neutrophilia (13.8t021.1 X 103/ml[normaI3.0to 11.5x 103/mlDinsix dogs, lymphopenia (0.4 to 0.9 X 103/ml [normal1.0 to 4.8 X 103/ m}]) in seven, and mild eosinophilia(1.3 to 1.8 X 103Iml [normal 0.1 to 1.2 X 103Iml])in three. Intestinal parasitism (whipworms) wassubsequently diagnosed in two dogs with eosinophil­ia. Serum chemistry abnormalities were noted in fiveof nine dogs and consisted of mild elevations of se­rum alkaline phosphatase, ALT (SGPT), and AST(SGOT). These findings were compatible with pre­vious glucocorticoid administration, because gluco­corticoid therapy is well known to alter liver enzymelevels in dogs.? Urinalyses were unremarkable in thethree dogs examined.

Skin biopsy specimens from all dogs were char­acterized by large, nonfollicular, subcorneal pustules(Fig. 4). Some specimens also contained small,intracorneai pustules. Evidence of concurrent super­ficial suppurative folliculitis was seen in 2 of the 13cases. Nondegenerate neutrophils accounted formore than 95% ofthe inflammatory cells present. Infour cases small to moderate numbers of acan­tho lytic keratinocytes were present but intragranu­lar acantholysis was not observed. The subjacent

Volume 22Number 6, Part 1June 1990 Canine and human subcorneal pustular dermatosis 1025

Fig. 4. Large subcorneal, intraepidermal pustule. (Hematoxylin-eosin stain; X25.)

Table I. Clinical findings in 13 dogs with sub corneal pustular dermatosis

Case No. Age (yr) Sex Breed Duration of disease

1 1 M Doberman pinscher 6 mo2 7.5 FS Irish setter 6 mo3 7.5 F Miniature schnauzer 2 yr4 10.5 FS Miniature schnauzer 1 yr5 4 M Boston terrier 4mo6 4.5 M Coonhound (black and tan) 2.5 yr7 7 F Miniature schnauzer Unknown8 8 FS Miniature schnauzer 16 rna9 9.5 M Miniature schnauzer 2mo

10 6.5 FS Labrador retriever 3 yr11 2 F Labrador retriever 2mo12 12 M Miniature schnauzer 1-2 yr13 2.5 F Samoyed 4mo

FS, Female spayed.

papillary dermis showed varying degrees of vasculardilatation and congestion, edema, and perivascularaccumulations of neutrophils, lymphocytes, histio­cytes, and occasional plasma cells. Eosinophils wererarely seen. Examination of acid orcein Giemsa­stained sections revealed extracellular and intracel­lular cocci in one dog.

Immunopathologic evaluation was performed in10 cases and consisted of direct immunofluorescencetesting (IgO, IgM, IgA, C3), indirect immunofluo­rescence testing (IgO, IgM, and IgA; dog tongueused as substrate), ANA test, lupus erythematosuscell test, and cellulose acetate serum protein electro­phoresis. Results of all tests were negative with theexception of a positive ANA at a significant titer(1:40) in one dog (case 5) and a variety of mild,

nonspecific alterations on serum protein electro­.phoresis. The most frequent findings were elevateda[-, iX2-, and ,6-globulins and decreased 'Y2-globulins.

Historical information regarding previous ther­apy was available for 12 of the 13 cases. Ten dogshad been treated with both systemic antibiotics andsystemic glucocorticoids, one dog had received anti­biotics only, and one dog had been treated with oralprednisone alone. Miscellaneous treatments in­cluded griseofulvin, thyroxine, megestrol acetate(Ovaban), and a variety ofdips and shampoos. Noneof these therapeutic agents had been of any signif­icant benefit.

Ten dogs were ultimately treated with dapsone(Avlosulfon) at an oral induction dosage of 1 mg/kgthree times daily. Dapsone was prescribed initially in

1026 Kalaher and Scott

Journal of theAmerican Academy of

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Table II. Treatment and therapeutic response in 13 dogs with subcorneal pustular dermatosis

6 Ampicillin, dapsone

7 None

8 Dapsone9 Dapsone

10 Dapsone

11 Dapsone

case No.

2

34

5

12

13

LFU, Lost to follow-up.

Treatment

Dapsone

Chloramphenicol,lincomycin,dapsone, sulfasalazine,sulfasalazineandprednisone

UnknownDapsone

Dapsone

None

Dapsone

Therapeutic response

Good response: Medication discontinued after 6mos. Dog relapsed and dapsone reinstituted foranother 6 mos. Therapy discontinued and dognormal for 5 yr before LFU

No response to antibiotics. Good response to dap­sone before development of dapsone drug erup­tion. No response to sulfasalazine with or with­out prednisone: Dog euthanized

Unknown (LFU)Good: Maintained with alternate-day therapy for

1 yr before LFUGood response: Relapse when medication discon­

tinued. Dapsone reinstituted and dog main­tained with alternate-day therapy for 2 yr be­fore LFU

No response to antibiotic. Good response to dap­sone; dog maintained with alternate-day ther­apy for 2 yr before LFU

Not treated: Euthanized due to deteriorating neu­rologicstatus

Unknown (LFU)No response: Dog euthanized 1 mo after initiation

of therapyGood response: Dog maintained with alternate­

day therapy for 2 yr before LFUGood response to induction dose: Induction dose

required daily for 6 mo before medication couldbe tapered. Therapy discontinued and dog nor­mal for 2 yr before LFU

Not treated: Died of perforating intestinal carci­noma

Good response: Maintained with alternate-daytherapy for 1 yr; therapy discontinued and dognormal for 1 yr before LFU

eight dogs and subsequent to unsuccessful antibiotictrials (administered on the basis of bacterial cultureand sensitivity results) in two dogs. Cases 7 (dog eu­thanized because of neurologic deterioration) and 12(dog died of peritonitis as a result of perforating in­testinal carcinoma) were not treated. Treatment in­formation was not available for one dog (case 3).

Follow-up information was obtained for 9 of the10 dogs treated with dapsone (Table II). With theexception of case 9, all dogs responded favorablywithin 1 to 4 weeks after initiating therapy. Therewas no apparent difference in response to dapsone onthe basis of age, breed, or sex of affected dogs. Inthree dogs long-term remissions (I, 2, and 5 years)occurred after discontinuation of 12- to I8-month

courses of dapsone. Four dogs received alternate-daymaintainance therapy (1 rug/kg once every otherday) for follow-up periods of 1 to 2 years. In thesedogs attempts to stop or decrease the frequency oftherapy resulted in the recurrence of skin lesions. Acutaneous drug eruption (generalized, pruritic,erythematous macules and papules) was diagnosedin one dog (case 2) early in the course of dapsonetreatment. When dapsone therapy was discontinuedthe maculopapular eruption disappeared but thesubcorneal pustular dermatosis recurred. This dogwas euthanized after an unsuccessful trial of oralsulfasalazine (Azulfidine) (20 mg/kg three timesdaily), alone and in combination with oral pred­nisone. No response was observed in case 9, and eu-

Volume 22Number 6, Part 1June 1990 Canine and human subcorneal pustular dermatosis 1027

thanasia was elected 1 month after the initiation ofdapsone therapy.

DISCUSSION

Although the similarities between human sub­corneal pustular dermatosis and its canine counter­part are numerous, notable differences are also ap­parent. In dogs there is no age or sex predilection.However, a definite breed predisposition exits for theminiature schnauzer. In human beings, althoughthere is no racial predilection, most cases of sub­corneal pustular dermatosis occur in middle-agedwomen.7, 8 In both species primary skin lesionscon­sist of nonfollicular pustules that have a tendency tocoalesce and to form annular or serpiginous patterns.The characteristic hypopyon formation seen in somehuman patients has not been observed in the dog. Inhuman beings symmetric involvementof the axillae,groin, abdomen , and flexor aspects of the limbs isobserved most cornrnonly.I-f The palms and solesare rarely affected, and the face, scalp, and mucousmembranes are never involved.7, 8 In dogs the distri­bution of the lesions is not as predictable. It appearsthat the trunk and head are most frequently af­fected. Although pruritus is not usually a prominentfeature of this condition in either species, occasion­ally human and canine patients may be intenselypruritic. The naturally occurring remissions and ex­acerbations characteristic of subcorneal pustulardermatosis in human beings have not been reportedin the dog. Systemic symptoms and laboratory ab­normalities are uncommon findings in dogs and inhuman beings unless a concurrentdisorder ispresent.

In dogs cytologic evaluation of direct smears fromintact pustules reveals nondegenerate neutrophils,few or no acanthocytes, and no microorganisms. Al­though bacterial cultures are usually negative, co­agulase-positive and coagulase-negative staphylo­cocci have occasionally been isolated in dogs and inhuman beings. I. 9, [0 Because antibiotic therapy hasbeen ineffective in these cases, the isolates were pre­sumably either normal cutaneous flora or contami­nant organisms.

Human and canine subcorneal pustular derma­tosis is characterized histopathologically by a sub­corneal intraepidermal pustular dermatitis in whichthe neutrophil is the predominant inflammatory cell.Although a small number of acanthocytes may bepresent in some cases, acantholysis isnot observed asa primary pathologic process.

Results of immunologic studies, including ANA,

direct immunofluorescence testing, and indirect im­munofluorescence testing, are generally negative indogs and in human beings. Sneddon andWilkinson11 observed IgA attached to leukocyteswithin a pustule in one case but acknowledged thatthis finding might have been artifactual. Intercellu­lar IgA deposition in the upper epidermis of perile­sional skin was reported in one patient,12 and IgA K

deposits were found in the subcorneal zone of perile­sional skin in another. 13 In the latter case investiga­tors alsodemonstrated a circulating monoclonal IgAK immunoglobulinreacting with the subcorneal zoneof normal human epidermis.13

Dapsone is the current treatment of choice in ca­nine and human subcorneal pustular dermatosis . Inboth speciessustained remissions rnay be observed insome patients after discontinuation of therapy. Inmost cases, however, maintenance dapsone admin­istration is required. Numerous side effects havebeen associated with dapsone use in humanpatients.!" In dogs reported adverse reactions in­clude blood dyscrasias (anemia, leukopenia, throm­bocytopenia), hepatotoxicity, vomiting, diarrhea,and a generalized erythematous, maculopapulareruption. 2, 14. 15 The development of leukopenia,liver enzyme elevation, and mild, asymptomaticanemia is frequently seen in dogs during inductiontreatment. These abnormalities usually resolveoncemaintenance dosages are achieved. Dapsone ther­apy has not been uniformly successful in either hu­man beings or in dogs. Systemic glucocorticoids,sulfapyridine, sulfisoxazole, UVB phototherapy, a­tocopherol (vitamin E), retinoic acid, and a retinoicacid derivative have been reported to be efficaciousin some human cases." 16·20 Systemic glucocorti­coids have been consistently ineffective in dogs, butthe other therapeutic modalities mentioned previ­ously have not been evaluated.

Although the etiology of subcorneal pustular der­matosis is unknown, it has been postulated that im­mune mechanisms may play a role in the patho­genesis of the disease. With the use of the immuneadherence test, in vivo immune complex formationin the stratum corneum was demonstrated in twohuman patients." The authors speculated that suchcomplexes might lead to the generation of a chemo­tactic factor, which would trigger neutrophil exocy­tosis and pustule formation. Ultrastructural studiesof perilesional skin have documented cytolysis of in­dividual keratinocytes in the granular cell layer.P Ithas been hypothesized that transepidermal leuko-

1028 Kalaher and Scott

cyte migration and subsequent subcorneal accumu­lations of cells are the result of cytolytic events oc­curring in the stratum granulosum.P In human be­ings a significant number of cases have beenassociated with the presence or subsequent develop­ment of paraproteinemia (with or without myelo­ma), which may obviously affect prognosis." Thesemonoclonal gammopathies are most frequently re­ported to be of the IgA type.t No such associationhas been observed in the dog.

As is the case in human beings, subcorneal pustu­lar dermatosis appears to be a rare disorder in thedog. During the past 12 years this conditionhas beendiagnosed in only 13of the more than 11,000 caninedermatologic cases evaluated at the New York StateCollege of Veterinary Medicine.

REFERENCES

1. Sneddon IB, Wilkinson DS. Subcorneal pustular dermato­sis. Br J Dermatol 1956;68:385-94.

2. Halliwell REW, Schwartzman RM, Ihrke PJ, et al. Dap­sone for treatment of pruritic dermatitis (dermatitis her­petiformis and subcorneal pustular dermatosis) in dogs. JAm Vet Med Assoc 1977;170:697-703.

3. McKeever PJ, Dahl MY. A disease in dogs resembling hu­man subcorneal pustular dermatosis. J Am Vet Med Assoc1977;170:704-8.

4. Scott DW, Wolfe MJ, Smith CA, et al. The comparativepa thology of non-viral bullous skin diseases in domestic an­imals. Vet Pathol 1980;17:257-81.

5. Baker KP. Subcorneal pustular dermatosis seen in dogs[Letter]. Vet Rec 1980;106:420.

6. Hirschberger J. Ein Fall von Subkornealer Pustuloser Der­matose nach imrnunhamolytischer Anarnie bei einem Mit­telschnauzer. Kleintierpraxis 1988;33:471-3.

7. Honigsrnann H, Wolff K. Subcorneal pustular dermatosis(Sneddon-Wilkinson disease). In: Fitzpatrick TB, Eisen

Journal of theAmerican Academy of

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AZ, Wolff K, et ai, eds. Dermatology in general medicine.New York: McGraw-Hill, 1987:601-4.

8. Rook A, Wilkinson DS, Ebling FJG, eds. Textbook of der­matology. Oxford: Blackwell, 1979; 1473-4.

9. Muller GH, Kirk RW, Scott DW, eds. Small animal der­matology. Philadelphia: WB Saunders, 1989:828-31.

10. McKeever PJ, Dahl MV. Subcorneal pustular dermatosis.Vet Clin North Am 1979;9:73-7.

11. Sneddon IB, Wilkinson DS. Subcorneal pustular dermato­sis. Br J Dermatol 1979;100:61-8.

12. Tagami H, Iwatsuki K, Iwase Y, etal. Subcorneal pustulardermatosis with vesiculobullous eruption: demonstration ofsubcorneal IgA deposits and a leukocyte chemotactic fac­tor. Br J Dermatol 1983;109:581-7.

13. Wallach D, Cottenot F, Pelbois G, et al. Subcorneal pustu­lar dermatosis and monoclonal IgA. Br J Derrnatol 1982;107:229-34.

14. Scott DW. Sulfones and sulfonamides in canine dermatol­ogy. In: Kirk RW, ed. Current veterinary therapy; vol 9.Philadelphia: WB Saunders, 1986:606-9.

15. LeesGE, McKeeverPJ, Ruth GR. Fatal thrombocytopenichemorrhagic diathesis associated with dapsone administra­tion to a dog. J Am Vet Mcd Assoc 1979;175:49-52.

16. Honeycutt WM, Jansen GT. Subcorneal pustular derma­tosis (subcorneal pustulosis of Sneddon-Wilkinson). In:Demis OJ, ed. Clinical dermatology. Philadelphia: Harper& Row, 1987:1-5.

17. Park YK, Park HY, Bang DS, et al. Subcorneal pustulardermatosis treated with phototherapy. Int J Derrnatol1986;25: 124-6.

18. Ayres S, Mihan R. Subcorneal pustular dermatosis con­trolled by vitamin E [Letter]. Arch Dermatol 1974;109:914.

19. Folkers E, Tafelkruyer J. Subcorneal pustular dermatosis(Sneddon-Wilkinson disease): therapeutic problems. Br JDermatol 1978;98:681-4.

20. Kaufmann J. Subcorneale pustulosis Sneddon-Wilkinson.Derrnatologica 1975;150:238-42.

21. Krogh HK, Tonder O. Subcorneal pustular dermatosis:pathogenic aspects. Br J Dermatol 1970;83:429-34.

22. Metz J, Schropl F. Elektroncnmikroskopische Untersu­chungen bei subcornealer pustuloser Dermatose. Arch KlinExp Dermatol 1970;236: 190-206.