Staphylococcal Apocrine Gland Infections in the Dog (Canine Hidradenitis Suppurativa)

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STAPHYLOCOCCAL APOCRINE GLAND INFECTIONS IN THE DOG (CANINE HIDRADENITIS SUPPURATIVA) By

ROBERT M. S C HWARTZMAN AND HENRY

G.

MAGUIR E

School of Veterinary Medicine, Division of Dermatology, University of Pennsylvania, and Hahnemann M edical College and Hospital , Section of Dermatology, Philadelphia, Pennsylvania

SUMMA RY

Four cases of a unique, extensive apocrine gland pyoderma in dogs are reported . This syndrome has not been described previously. It is characteri zed by the following features. Distributio"n: inner thighs, groin, scrotum or vulva, axilla. Appearance of lesions: suppurative, sharply-marginated, erythematous, nontender, warm plaques. 3. Surface e xudate: PMN's with phagocytized bacteria; culture shows coagulasepositive, haemolytic staphylococci. 4. General health of animals: good. 5. Course: treatment induced only temporary remissions; three of four dogs euthanized, disease active in remaining animal. 6. Histology: inflammation and variable destru c tion~ of apocrine glands and periapocrine tissue. Infections of apocrine glands in man and dog are discllssed from a comparative point of view. I.

2.

Pyogenic infection of the apocrine gland in man (hidradenitis suppurativa) is a well-defined disorder that is a frequent subject of clinical reports and case presentations. Though the dog has similar apocrine structures which are distributed on all hairy skin, infections of canine apocrine sweat glands have not been reported. In fact, there are no r eports in the literature of apocrine gland infections in any domestic animal. Human hidrad enitis suppurativa is a chronic recurrent progressive bacterial infection originating in apocrine glands and extending from there to surrounding tissues. The axillae and groin, which are areas of highest apocrine gland concentration, are the commonly affected sites. The involvement tends to be symmetrical (Rostenberg & Diamond, 1962). The infection produces much pus and results in a characteristically destructive and hypertrophic scarring. Well-developed cases are diagnosed easily by physical examination alone. In early cases, the differential diagnosis includes furunculosis, granuloma (especially zirconium), contact dermatitis, eccrine miliaria, tuberculosis, Fox-Fordyce disease, malignancy (lymphoma, metastatic disease), d eep mycoses, and r eactive lymphadenopathy.

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Staphylococcus aureus is responsible for the disease in nearly all human cases. While usually the general health of the patient is not affected, occasionally hidradenitis suppurativa has grave implications. Fistulae to internal organs may develop and, rarely, death may result (Brunsting, 1939; Moschella, 1966). The disease affects young adults. The unripe apocrine apparatus of the infant as well as the withering apocrine glands of the middle-aged and older adult are generally exempt. Disease of the pilosebaceous apparatus, as expressed by severe acne and/or dissecting folliculitis of the scalp (perifolliculitis abscedens et suffodiens), often is associated; and a related pathophysiology, perhaps, is involved in these disorders of skin appendages (Brunsting, 1939). Unlike the female favouring of Fox-Fordyce's disease, human hidradenitis suppurativa shows no predilection for either sex. The disease lingers and resists treatment; recurrence is the rule (Omens, Omens & Latoni, 1959; Brody, 1962; Rostenberg & Diamond, 1962; Harrison, 1964). In early cases vigorous use of systemic antibiotic and cleansing antibacterial topical medicaments are sometimes curative. However, the cicatrized wound of long-standing hidradenitis suppurativa generally presents too felicitous a home for pathogenic bacteria to be controlled permanently by antibacterial agents. Permanent cure often requires radical excision of diseased tissue. The purpose of the present report is to describe the clinical and histopathologic findings related to hidradenitis suppurativa in the dog and to compare it with the disease that occurs in man. Of 1500 dermatological cases registered at the Veterinary Clinic of the University of Pennsylvania over a 3-year period, 100 were pyodermas; of these, four were apocrine gland infections (histologically confirmed) . The clinical manifestations of the infection in these four cases were similar and strikingly different from that of all other canine pyodermas. Pyogenic apocrine gland infections in the dog appear to represent a distinct clinically recognizable syndrome with a unique course and identifiable histopathology. CASE REPORTS

The age, breed, and sex of the four dogs are presented in Table I. The clinical and histopathologic findings were so similar in the four cases that they will be reported as one. TABLE I DETAILS OF FOUR CANINE CASES OF HIDRADENITIS SUPPURATIVA

Age (years) II

2! 3 8

Breed Mongrel Shetland sheepdog Shetland sheepdog Shetland sheepdog

Sex Female Male Female (spayed) Ma le

The most striking lesions were on the thin-skinned areas, especially the inner thighs, groin, scrotum or lips of the vulva, abdomen and axilla. The

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lesions were oozing, suppurative, erythematous plaques (raised 2- 3 mm.) of various sizes and shapes (Figs. I and 2). The plaques were sharply marginated, non-tender, and warm. Smears from the surface exudate contained polymorphonuclear leucocytes with phagocytized bacteria. Coagulase-positive haemolytic Staphylococcus aureus was cultured from all four cases (see Table II for antibiotic sensitivity). Cultures and scrapings for fungus were always negative. On the face of the animals, there were circular crusted ulcers, usually less than ten in number, containing coagulase-positive haemolytic Staphylococcus aureus. Other evidence of pyoderma seen in the four patients included: (I) an ulcerative stomatitis (coagulase-positive haemolytic Staphylococcus aureus) ; (2) cheilitis and, (3) otitis extern a (Proteus vulgaris in two of the four cases). TA BL E II ANTIBIOTIC SENSITI V ITY

OF COA GUL A SE -POSIT I VE S taphylococcus aureus ISO LATED C ANIN E CASES O F HIDRA DENITIS SU PP U R A TI V A

Case Pen icillin Strep tomycin T etracycline Sulfo namides itrofurantoin Chloramphenicol Neomycin Erythrom ycin Bacitracin Polymyxin T riacetyloleandomycin Meth icill in

Case

I

2

Cases

Sligh t

+ + +

Not run

FOUR

Case 4

Sligh t

+ +

Slight

+ +

Not run

Slight

F ROM

-+

+ +

+

Although skin lesions were quite extensive, the animals were not visibly distressed by them; the dogs were apparently well in terms of general h ealth (eating, eliminations, activity etc.). Physical examinations were negative, except for occasional regional adenopathy. A const~nt complaint of the owners was that the animal constantly licked the lesions. Despite vigorous therapy, the disease was never entirely eradicated in any of the dogs. The treatment schedules are summarized in Table III. T ABLE HI RESULTS OF TREATMENT OF F O U R

CANIN E CAS E S OF H I D R ADEN I T I S SUP P U R ATIV A

Agents employed N itrofurantoin ; triacetyloleandomycin; ph isohex ba ths ; autogen ous bacterin Meth icillin ; triacetyloleandom ycin ; p h i. sohex baths; n eomycin , bacterin and polymyxin o intment topically T riacetyloleandom ycin; prednisolon e; ph isohex washings Triacetylolean dom ycin; prednisolone; autogenous bacterin

Duration 7 months 6 weeks 7 weeks 12

months

Results Periods of improvement never comp lete clearing: killed Abdomen and mou th com p letely cleared (otitis externa, non-responsive to treatment) Sligh t improvemen t, remission : killed Periods of improvement, never comp lete clearing: killed

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Tissue for histopathologic study was obtained by biopsying erythematous plaques on the abdomen. The tissues were fixed in formalin and stained with H & E, PAS, and Gram's stain. The epidermis was ulcerated in all sections studied. In the upper one-quarter of the dermis, there was a chronic inflammatory reaction. Vascular dilatation and a fibroblastic reaction were prominent (Fig. 3). In the remainder of the dermis and subcutis, apocrine structures were either filled with, or surrounded by, inflammatory exudate (Figs. 4 and 5). There was occasionally an apocrine structure which had ruptured or lost its normal architecture. The infiltrate which aggregated in and around the apocrine structures was predominantly polymorphonuclear. In Gram-stained sections, Gram-positive cocci were seen in the inflammatory exudate in and around the apocrine structures and in the surface reaction. PAS stained sections were negative for fungi. DISCUSSION

It is enigmatic that hidradenitis suppurativa in dogs is not common when one considers that apocrine glands are almost universally distributed on canine skin, and that primary staphylococcal pyodermas are a frequent cause for presentation of an animal to a veterinary clinic. The apocrine glands of man and dog have many similarities. In both species, functional activity of the glands occurs at puberty (Roy, 1954 ; Schwartzman & Orkin, 1962), and the glands are under dual autonomic control, being stimulated by intradermal injections of both adrenalin and acetylocholine (Aoki & Wada, 1951 ). Infusions of adrenalin and noradrenalin cause generalized sweating in the dog, and the hydro tic response occurs equally in sympathectomized and normally innervated areas (Iwabuchi, 1967). Generalized sweating also is induced by asphyxiation in the dog; and this sweating is not abolished by bilateral, adrenal medullectomy, and does not occur in sympathetically denervated skin. Thus, in the dog, both humoral and nervous mechanisms play a role in controlling the apocrine gland. In addition, it has been reported that the application of heat to canine skin results in profuse local sweating (Aoki & Wada, 1951). As this occurs in denervated skin, it is assumed that heat acts directly on the gland. The canine apocrine apparatus structurally contrasts with that of man, in that it is less developed, contains less pigment and no iron, has a lower secretory epithelium, and has a duct that opens into the follicle at a higher level (Schwartzman & Orkin, 1962) than its human counterpart. The pathogenesis of hidradenitis suppurativa in the dog has not been studied; in man the disease may represent an uncommon sequella of apocrine anhidrosis. Shelley & Cahn (1955) induced hidradenitis suppurativa in the axilla of healthy adult males by the application of perforated belladonna tape over several weeks. The first abnormality noted was obstruction of the apocrine duct by a keratin plug; this coincided with clinical anhidrosis. The duct below the obstruction then became filled with apocrine secretion, and trapped surface bacteria proliferated in this stagnant secretion. Inflammation of the lower duct and gland resulted; followed by extension to surrounding tissue,

PLATE I

Fig.

I.

Sharply marginated, erythematous suppurative plaques on groin .

Fig.

2.

Similar lesions as in Fig.

1

on axilla.

Schwartzman and Maguire, B1". vet. ]. ( 1969),

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PLATE II

Fig. 3. The epidermis is ulcerated and granulation tissue occupies the upper aspects of the d ermis. Note apocrine structure fill ed with inflammatory infiltrate to the right of centre. H&E, x 45.

Schwartzman a nd Maguire, Br. vet. ]. (1969), 125, 3

PLATE III

Fig. 4. A mixed inflammatory infiltrate aggregates around apocrine stru ctures deep in the d ermis. H&E, X 100.

Schwartzman and Maguire, B1". vet. ]. ( 1969), U5, 3

PLATE IV

Fig·5 a .

Fig·5 b . Fig. 5. Inflamma tor y cells, predominantl y polymorphonuclear, are present within the lumen of a n a pocrin e stru cture. H&E, X 100 and 450 .

Schwartzman a nd Mag uire, 8 r. vet.

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i.e., hydradenitis suppurativa. Simple occlusion with resulting axillary anhidrosis in the absence of bacteria did not produce inflammation. Apocrine gland infections in man and dog share certain clinical similarities : (I) chronic course; (2) resistance to therapy; (3) staphylococcal causation; and (4) usual absence of systemic manifestations. The lesions, however, are distinctly different : erythematous plaques in dogs; and nodules, hypertrophic scars and fistulae in man. While malodour often is associated with the infection in man, it is not noted in the dog. The histopathologic reactions differ also; though in both man and dog, inflammation in and around the apocrine structures is a striking and characteristic feature of the disease. It is on the basis of the apocrine gland involvement in the canine disease (not found in biopsy material from other canine pyodermas) that the authors chose to term the disease in dogs hidradenitis suppurativa. In man, the earliest histopathological change is located in the subcutaneous tissue and is characterized by an inflammatory reaction in and around apocrine glands (Lever, 1954). The infiltrate is composed predominantly of polymorphonuclear leucocytes with occasional lymphocytes, plasma cells, and foreign body giant cells. Gram-positive cocci can be identified in the polymorphonuclear leucocytes. As the process advances, the inflammatory reaction extends to the surrounding tissue. Tissue from well-developed lesions usually shows a non-diagnostic picture of massive destruction and cicatrization. By contrast, in dogs, the most intense reaction is superficial. The surface epithelium is ulcerated and the upper one-third of the dermis showed a chronic inflammatory reaction (fibroblastic and prominent vascular dilatation). The lower aspects of the dermis and sub-cutis show little change other than an inflammatory reaction in and around apocrine structures. As in experimentallyinduced hidradenitis suppurativa in man, the disease process in the dog appears to extend from the surface downward into the lower apocrine structures. Whether or not the intense inflammatory reactions observed in the subcutaneous and lower dermis of man would develop in the canine patient with progression of the disease is a moot point. To the authors' knowledge, the suppurative plaques described in the four cases of this report are a strikingly different manifestation of a staphylococcal infection of canine skin than that which occurs in other primary pyodermas. The lesion of impetigo in the dog is a superficial pustule (6-8 mm. in diameter) on an erythematous base. Superficial folliculitis is characterized by an erthematous papule, papulo-pustule, pustule or an annular plaque (resembling the lesion ofringworm). In furunculosis, the usual lesion is a flocculant (cystic) or firm nodule with apical suppuration or ulceration. Juvenile pyoderma is characterized by a cellulitis of the lips and the usual secondary pyoderma of the dog (hotspot, moist eczema, pyo-traumatic dermatitis) by a discrete circular erythematous a nd suppurative infiltrated patch. It is worth emphasizing again, that involvement of apocrine structures in pyodermas other than hidradenitis suppurativa is not a usual histopathologic finding. It is expected that as more cases of canine hidradenitis suppurativa are looked for, they will be recognized and described. ,t\' orthy of emphasis is the

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apparent predisposition of the Shetland sheepdog for the disease. It is likely that a comparable syndrome occurs in other domestic species of animals; and that canine hidradenitis suppurativa could be a useful model for study of the human disease. ACKNOWLEDGMENT

This investigation was supported (in part) by a Public Health Service research career programme award (K-No.- AM- I6,6oo) from the Institute of Arthritis and Metabolic Diseases. REFERENCES

AOKI, T. & WADA, M. ( 1951 ). Science, N.Y., 1140 123-124. BRODEY, M. (1962). Archs D ermat., 86, 362-363. BRUNSTING, H. A. (1939). Archs Dermat., 39, 108-120. HARRISON, S. H . (1964). Br. J. plast. Surg., 17, 95-g8. IWABUCHI, T. (1967). J. invest. Derm. , 49, 61 - 70. LEVER, W. F. (1954). Histopathology of the Skin, 2nd edn, pp. 169-17°' Philadelphia; J. B. Lippincott. MOSCHELLA, S. L. (1966). J. Am. med. Ass., 19B, 201-203. OMENS, D. V., OMENS, H. D. & LATONl, j. (1959). Archs D ermat., So, 146-147. ROSTENBERG, A. & DIAMOND, S. (1962). Archs Dermat., 86, 243-244. RoY, W. E. (1954). J. Am. vet. med. Ass., 1240 51. SCHWARTZMAN, R. M. &,ORKIN, M. (1962). A Comparative Study o/Skin Diseases of Dog and Man, pp. 24-38. Springfield, Illinois: Charles C. Thomas. SHELLEY, W. B. & CAHN, M. M. (1955). Archs Dermat., 72, 562-565. (Accepted/or publication 6 August 1968)

Inlectiones staphylococciques de la glande apocrine chez Ie chien (hidradenite canine purulente) (SchwartzIDaD et Maguire) ResUD1e. On a communique quatre cas d'une pyodermie unique et etendue de la glande apocrine chez les chiens. Ce syndrome n'a pas ete decrit auparavant. II est caracterise par les traits suivants: I. Repartition: l'interieur des cuisses, l'aine, Ie scrotum ou la vulve, l'aisselle. 2. Aspect des lesions: plaques purulentes, nettement marginees a erytheme, non douloureuses a la pression, chaudes. 3. Epanchement de surgace: de PMN avec bacteries phagocytees. la culture montre des staphylocoques hemolytiques, positifs a la coagulase. 4. Sante generale des animaux: bonne. 5. Cours: Ie traitement ne donna lieu du'a des remissions temporaires; trois des quatre chiens tues, la maladie etant active chez l'animal restant. 6. Histologie: inflammation et destruction variable des glandes apocrines et des tissus les entourant. On diecute a present des infections des glandes apocrines chez l'homme et Ie chien, d'un point de vue comparatif. Staphylokokkal-Apocrindriisen-Infektionen bei Hunden (Canine Hidradenitis Suppurativa) (SchwartzD1an und Maguire) Zusa~enfassung. Vier FaIle einer einzigartigen ausgedehten Apocrin-Driisenpyoderma bei Runden werden behandelt. Dies Syndrom wird zum ersten mal beschrieben. Es ist folgendermassen charakterisiert: I. Betroffene Teile: innere Oberschenkel, Leistengegend, Skrotum oder Vulva axilla.

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Ausseh en der betroffenen Stellen: suppurativ, scharf begrenzt, Erythmea, nicht schmerzende, warme Stellen. 3. Oberflachenabsonderung: PMN mit phagozytizierten Bakterien. Die Kultur ist Coagulase-positiv und zeigt hamolytische Staphylokokken. 4. Allgemeiner Gesundheitszustand der Tiere: gut. 5. Verlauf: Behandlung bewirkte nur zeitweises Abklingen, drei der vier Hunde starben, bei dem vierten Tier ist die Krankheit weiterhin aktiv. 6. Histologie : Entziindung und unterschiedliche Zerstbrung der Apocrindriisen und des eryapocrinen Gewebes. Infektionen der Apocrindriisen beim Menschen und beim Hund werden vergleichend erbrtert. 2.

Infecciones e s tafiloc6ccicas de la glandula apocrina en el perro (hidradenitis supurativa caniDa) (SchwartzD1lln y Maguire) Res UDlen. Se informa sobre cuatro casos de una pioderma extensa y sin igual de la gla.ndula apocrina en perros. Este sindrome no ha sido descrito anteriormente. Es caracterizado por los siguientes factores : I. Distribuci6n: muslos interiores, ingle, escroto 0 vulva, axila. 2. Aspecto de las lesiones: supurativas, distintamente marginadas, eritematosas, no tiernas, plaquetas calientes. 3. Exudado de la superficie: PMNs con bacterias fagocitizadas; la cultura revela estafilococos hemoliticos coagulasopositivos. 4. Salud general de los animales: buena. 5. Curso: el tratamiento indujo tan solo remisiones temporaneasj de los cuatro perros, se mataron tres, continuando activa la enfermedad en el animal restante. 6. Histologia: inflamaci6n y destruccion variable de las glandulas apocrinas y de los tejidos periapocrinos. Se exponen las infecciones de las glandulas apocrinas en el hombre y en el perro desde un punto de vista comparativo.