History
A 7-year-old 32.4-kg (71.3-lb) castrated male Golden Retriever was initially evaluated because of a sudden onset of cutaneous, multifocal, raised, erythematous, plaque-like lesions. The dog was actively enrolled in a study to evaluate the use of platelet-rich plasma to improve osseous healing following tibial plateau leveling osteotomy; the skin lesions developed 7 weeks after surgery. Immediately after surgery, the dog received carprofena (2.3 mg/kg [1.0 mg/lb], PO, q 24 h for 7 days), cephalexinb (30 mg/kg [13.6 mg/lb], PO, q 8 h for 7 days), tramadolc (3 mg/kg [1.4 mg/lb], PO, q 8 h for 7 days), and trazodoned (8 mg/kg [3.6 mg/lb], PO, as needed); all medications were discontinued 2 weeks prior to development of skin lesions.
Clinical and Gross Findings
On physical examination, the dog was bright, alert, and responsive with abnormalities limited to the integument. Dermatologic examination revealed multifocal, well-circumscribed erythematous plaques and nodules, which were located in the right temporal region at the ear base, around the right eye (Figure 1), on the proximal aspect of the right scapula and left lateral aspect of the muzzle, and 4 cm from the dorsal midline bilaterally (at the thoracolumbar junction). There was no associated pruritus, signs of pain, ulceration, or alopecia. Cytologic examination of a fine-needle aspirate specimen from a single lesion revealed a large number of neutrophils but no evidence of infectious agents. Four 8-mm-diameter punch biopsy specimens were obtained from the periocular and thoracic skin lesions and submitted for histologic examination.
Photographs of the right periocular region (A) and left lateral aspect of the thoracolumbar junction (B) in a 7-year-old Golden Retriever. Around the right eye, there are 3 well-circumscribed, raised, erythematous, and alopecic nodules; 2 nodules are deforming the upper eyelid, and 1 nodule is associated with the lower eyelid. On the left lateral aspect of the thoracolumbar junction, there are 3 well-circumscribed, erythematous, raised annular plaque-like lesions with central clearing.
Citation: Journal of the American Veterinary Medical Association 256, 10; 10.2460/javma.256.10.1119
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic Findings
Microscopic examination of sections of the routinely processed biopsy specimens revealed a densely cellular inflammatory infiltrate that had effaced most of the dermis and extended into the subcutis (Figure 2) The infiltrate consisted predominantly of epithelioid macrophages and neutrophils with fewer lymphocytes and plasma cells, consistent with a pyogranulomatous inflammatory response. Dermal infiltrates surrounded and effaced hair follicles and adnexal structures, forming a pattern of thick, regularly spaced, vertically oriented, finger-like bands of inflammation (sausage-shaped pattern). The few remaining follicular structures were atrophied; however, despite the marked periadnexal pattern of inflammation, infiltration of the follicular epithelium itself was rare. Within the subcutis, the inflammation formed coalescing nodules centered around blood vessels. Edema and small scattered areas of necrosis were present throughout the lesions. No etiologic agents or foreign material was present on H&E-stained sections. Acid-fast, modified acid-fast, Gram, and Gomori methenamine silver staining of sections also revealed no infectious organisms. Paraffin-embedded sections from formalin-fixed tissue underwent real-time PCR assays for Leishmania spp and Mycobacterium spp DNA, which yielded negative results.
Photomicrograph of a section of a biopsy specimen obtained from one of the dog's skin lesions. Notice the thick, densely cellular bands of pyogranulomatous inflammation that surround atrophied hair follicles (asterisks) and form vertically oriented sausage-shaped projections throughout the affected dermis. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 256, 10; 10.2460/javma.256.10.1119
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: marked chronic pyogranulomatous periadnexal dermatitis and panniculitis in the haired skin of a dog.
Comments
For the dog of the present report, the collective findings of clinically distinctive erythematous plaques and nodules, cytologic detection of neutrophils without infectious agents in a fine-needle aspirate specimen, and the histopathologic evidence of pyogranulomatous lesions with a prominent periadnexal (sausage-shaped) pattern along with the absence of evidence of microbial agents (as determined by use of special stains on sections of skin punch biopsy specimens and results of PCR assays for Leishmania spp and Mycobacterium spp DNA) led to the diagnosis of cutaneous sterile pyogranuloma-granuloma syndrome (SPGS).
Cutaneous SPGS develops in dogs of any age and breed; male dogs seem to be overrepresented.1,2 Although SPGS can affect any breed, Weimaraners, Great Danes, Boxers, Golden Retrievers, English Bulldogs, Doberman Pinschers, and Dachshunds are more frequently affected.2 Initial cutaneous lesions consist of multiple firm, commonly nonalopecic, and erythematous papules, plaques, and nodules of various sizes (maximum dimension from 2 mm to 3 cm) that affect predominantly the skin of the head (mainly along the bridge of the nose, on the muzzle, and in the periocular regions) and interdigital areas and, less commonly, the pinnae, trunk, and abdomen.1,2 Skin lesions are usually without signs of pain or pruritus; however, in large heavy breeds (eg, Weimaraner, Great Dane, Boxer, and English Bulldog), the interdigital lesions may develop draining tracts, ulcerations, associated pruritus, and secondary infection.2 The most relevant clinical differential diagnosis is interdigital follicular cysts syndrome, which also affects the aforementioned large breeds of dog and features pyogranulomatous, nodular, ulcerative, and draining skin lesions in the interdigital skin areas with possible secondary infection.3 In the case described in the present report, multifocal, well-circumscribed erythematous plaques and nodules without alopecia developed acutely on the head and dorsal aspect of the thorax of a Golden Retriever; there were no interdigital lesions present.
A major histologic feature of early cutaneous SPGS is the vertically oriented, moderate to severe, pyogranulomatous inflammation (neutrophils and macrophages) that tracks the hair follicles in a sausage-shaped or nodular pattern; however, luminal folliculitis is not present.1,2,4 Older lesions consist of discrete to confluent granulomas (sparse neutrophils) and pyogranulomas (centrally located neutrophils and peripheral cuffs of macrophages) that obliterate adnexal structures and extend from the dermis to the deep subcutis.1,2,4 Lymphocytes and plasma cells are involved in small numbers, and normal to acanthotic epidermis with occasional ulceration is present.1,2,4 For the dog of the present report, the histopathologic appearance of the lesions was typical of SPGS with long, finger-like projections of pyogranulomatous inflammation surrounding, but not infiltrating, hair follicles and their adnexal structures.
Although the etiopathogenesis of SGPS is not known, an immunologic mechanism is suspected on the basis of negative results of microbial cultures of skin specimens and special staining of skin sections for microbial agents, the absence of foreign material detected by polarization microscopy, and a good response of affected dogs to immunomodulating agents.2,4–6 Because neutrophils and macrophages are involved in the formation of cutaneous SPGS lesions, it is tempting to postulate that an abnormal cellmediated immune response to an infectious agent or derived residual antigen is involved in immune activation of cutaneous SPGS at some point in the development of the lesions.2,4–6
Although pyogranulomatous inflammation is the major histopathologic finding in cutaneous SPGS lesions, it is also found in many other diseases that have a similar clinical appearance. There are bacterial, fungal, parasitic, foreign material-related, and idiopathic causes of granulomatous and pyogranulomatous nodular dermatitis in dogs.4,5 Because cutaneous SPGS is a diagnosis of exclusion, histologic examination of sections of affected skin after application of appropriate special stains (eg, Giemsa, Gram, periodic acid-Schiff, and Ziehl-Neelsen stains), examination of skin sections with polarized light microscopy (to detect foreign material),7 bacterial and fungal cultures of skin specimens, or real-time PCR assays to detect infection with Leishmania spp and Mycobacterium spp is recommended. In a retrospective study7 performed in Italy, real-time PCR assays were used to identify Leishmania spp DNA and Serratia marcescens DNA in 4 and 2 of 40 dogs with sterile pyogranulomatous nodular dermatitis, respectively. Leishmaniosis is endemic in > 70 countries in the world, and the organisms are present in high numbers in South and Central America, the Middle East, the Mediterranean (eg, Italy, Croatia, Spain, Israel, and Greece), and Portugal. Although rare in the United States, canine leishmaniosis is considered endemic in Texas. Other reported cases in the United States are infrequent and involve dogs traveling from Leishmania-endemic areas.8 These findings (particularly important in endemic areas) would necessitate the use of a real-time PCR assay of tissue specimens in addition to application of special stains to tissue sections to rule out Leishmania infection as a cause of the skin lesions. In the case described in the present report, no etiologic agents were visible in skin tissue sections treated with H&E, acid-fast, modified acid-fast, Gram, or modified Gomori methenamine silver stain. Furthermore, no Leishmania spp or Mycobacterium spp were detected by PCR assays of formalin-fixed tissues.
Given the postulated etiopathogenesis of cutaneous SPGS and the condition's lack of response to antimicrobial treatment, immunosuppressive intervention is considered the mainstay of treatment, following which lesions resolve in most dogs within 3 to 6 weeks.1,2,5 A review of published reports (56 cases) of cutaneous SPGS in dogs revealed that all but 4 dogs were administered immunosuppressive dosages of prednisone (2.0 to 4.4 mg/kg/d [0.9 to 2.0 mg/lb/d], PO) alone or with antimicrobials (doxycycline, enrofloxacin, amoxicillin, cephalexin, erythromycin, and cyclosporine in any combination).1,2,6,9 Four of the 56 dogs received less commonly administered immunosuppressive treatments, such as azathioprine2 or tetracycline with niacinamide,8 which resulted in similar responses. For the dog of the present report, topical chlorhexidine spraye was applied to areas of affected skin because treatment with systemic immunomodulators was not feasible owing to the dog's participation in the tibial plateau leveling osteotomy study. During a follow-up examination of the dog 3 weeks later, most SPGS lesions had completely resolved, and full remission was achieved in the following 2 weeks (ie, 5 weeks after the time of diagnosis). At 15 months after the time of diagnosis, no lesions had recurred in this dog.
The prognosis for dogs with cutaneous SPGS is good, and clinical remission is frequently achieved. Most lesions in affected dogs resolve between 3 and 6 weeks after commencement of immunosuppressive treatment.1,2,9 Remission in 2 dogs was achieved after 2 weeks of immunosuppressive treatment2; however, 1 dog underwent treatment for 6 weeks without full remission. Among the 24 dogs for which clinical remission was achieved, relapses developed in 8 dogs; all those dogs had responded well to the initial immunosuppressive treatment, and those that relapsed regained remission with the reintroduction of long-term immunosuppressive treatment. To the authors' knowledge, this is the first case report of a dog with cutaneous SPGS that resolved without systemic immunosuppressive treatment.
Footnotes
Carprofen, Zoetis Animal Health, Parsippany, NJ.
Cephalexin, Teva Pharmaceuticals, North West, Pa.
Tramadol, Amneal Pharmaceuticals LLC, Bridgewater, NJ.
Trazodone, Teva Pharmaceuticals, North West, Pa.
Chlorhexidine gluconate 4%, TrizEDTA, Dechra, Leawood, Kan.
References
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4. Gross TL, Ihrke PJ, Walder EJ, et al. Noninfectious nodular and diffuse granulomatous and pyogranulomatous diseases of the dermis. In: Skin diseases of dog and cat: clinical and histopathologic diagnosis. 2nd ed. St Louis: Mosby-Year-book, 2005;320–340.
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