Severe Ulcerative and Granulomatous Pinnal Lesions with Granulomatous Sebaceous Adenitis in Unrelated Vizslas
Granulomatous sebaceous adenitis (GSA) is uncommon in dogs; however, certain breed predilections exist. In this report, three cases of GSA in unrelated vizslas have been described. All cases initially presented with episodes of otitis externa followed by severe inner pinnal lesions. In one case, multifocal coalescing inner pinnal ulceration appeared 4 wk prior to the occurrence of the skin lesions. The other two cases presented with simultaneous pinnal and skin lesions following episodes of bilateral otitis. The pinnae were diffusely erythematous and had multiple coalescing erosions and ulcers. The body lesions consisted of multifocal alopecia, papules, and fine scales. Biopsies of the skin and pinnae confirmed GSA. Two dogs responded to treatment with synthetic retinoids and cyclosporin A, respectively. One dog was not treated, and the owners preferred euthanasia when the ear lesions recurred and did not respond to glucocorticoids. To the best of the authors’ knowledge, GSA with multifocal coalescing ulcerative pinnal lesions has not previously been reported.
Introduction
Granulomatous sebaceous adenitis (GSA) is an uncommon disease in dogs; however, certain breeds are predisposed to GSA, and its manifestations may differ within breeds.1,2 In the vizsla, the lesions usually begin as asymptomatic annular areas of scaling and alopecia with fine white nonadherent scales.2 The diagnosis of GSA is confirmed histologically with various degrees of granulomatous to pyogranulomatous sebaceous adenitis. In most cases, the sebaceous glands are no longer visible within the granulomas. Mild cases can be managed with topical keratolytic shampoo, propylene glycol spray, and nutritional supplementation with omega 3 and 6 fatty acids. Either synthetic retinoids or cyclosporine is recommended in more severe cases.1,2 This report describes three cases of GSA in unrelated vizslas in which the disease began with severe ulcerative pinnal lesions following otitis externa.
Case Report
Case 1
A 4 yr old spayed female vizsla presented with severe ulcerative otitis externa to the Dermatology Department at the Veterinary Teaching Hospital (VMTH), Koret School of Veterinary Medicine. The dog had previously been treated by the referring veterinarian with marbofloxacina ear drops for recurrent otitis externa, and the dog had responded well. When the otitis externa recurred and did not response to treatment with the same ear drops, the dog was treated with systemic cephalexinb (25 mg/kg per os [PO] q 12 hr for 2 wk) and Surolanc. An elimination diet trial was ineffective, and when the dog's condition deteriorated, the dog was referred to the VMTH.
General physical examination was unremarkable on presentation except for the severe multifocal coalescing ulcerative lesions on the inner aspect of the pinnae, which were very painful (Figure 1). There was a mild leukopenia (4.37×109/L; reference range, 6–17×109/L) on complete blood count (CBC). All other CBC, serum biochemistry, and urinalysis parameters were normal. The ears were examined under general anesthesia with isofluraned. The distal portion of the vertical ear canal revealed multifocal ulceration. An adverse reaction to either aural medication or to systemic antibiotics was suspected. Skin samples of areas adjacent to ulcers and erosions were obtained for histologic evaluation. Histopathology results were consistent with sterile granuloma (after no microorganisms were detected by periodic acid-Schiff and acid-fast stains). The granulomatous lesions were described as diffuse rather than perifollicular. The dog was treated with prednisonee (2 mg/kg PO q 24 hr) with marked improvement within 2 wk. Four weeks later, while on prednisone (1 mg/kg PO q 24 hr), the lesions in the inner pinnae had improved (Figure 2), but multifocal annular to coalescing alopecia was observed on the outer pinnae, head, neck, and trunk (Figure 3). Skin scrapings and fungal culture from the alopecic areas were negative for both mites and fungi. Two weeks after discontinuing prednisone, lesions from the head and trunk were sampled, and the biopsies were submitted for histologic evaluation. Histologically, the lesions were similar in all sections with minimal variations in intensity. Sebaceous gland lobules were absent throughout the sections. Nodular perifollicular aggregations of macrophages and few neutrophils were evident. The lesions were typical of GSA (Figure 4).
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Treatment with systemic synthetic retinoids or cyclosporine was declined by the owners due its high cost. One year later, the dog was euthanized due to recurrence of the severe inner pinnal lesions and lack of response to glucocorticoids.
Case 2
An 8 yr old spayed female vizsla presented to the VMTH for evaluation of hair loss on the head and severe ear pain associated with otitis externa. The dog had no history of medical problems until 1 mo prior to presentation when the dog had been diagnosed by the referring veterinarian with bilateral otitis externa. The ear infections were successfully treated with topical ear dropsf (q 12 hr for 10 days). Ten days prior to presentation, the owners noticed severe ear pain and hair loss on the head. The referring veterinarian prescribed cephalexin (20 mg/kg PO q 8 hr), but the condition deteriorated. On presentation to the VMTH, the physical examination was unremarkable except for the skin and ear lesions. The inner ear pinnae were diffusely erythematous with multifocal crusts and erosions (Figure 5). The body lesions consisted of multifocal alopecia, papules, nodules, and fine scales, especially on the head and between the scapulae. The ears were examined under general anesthesia maintained with isoflurane and oxygen. Diffuse erythema of the ear canals with severe purulent discharge was noted, and the left tympanic membrane was ruptured. Neutrophils, cocci, and rods were present on cytology smears from the ear canals and pinnae. Follicular casts were observed on trichography of the skin lesions. Skin scrapings were negative for mites, and the CBC and blood chemistry were normal. Biopsy samples from alopecic areas of skin and erythematous areas of the pinnae were taken for histology. The lesions were similar in all samples submitted but with marked variations in intensity. Perifollicular granulomas at the level of the isthmus composed of macrophages and few neutrophils were noted. Sebaceous gland lobules were absent. In sections, including the aural samples (Figure 6), no organisms were observed on routine hematoxylin and eosin staining. The findings in the body skin samples were typical of GSA. The dog was initially treated with cephalexin (25 mg/kg PO q 12 hr for 4 wk) and ofloxacing (10 mg/kg PO q 24 hr for 4 wk) based on culture and susceptibility test results, and prednisone (at a starting dose of 2 mg/kg PO q 24 hr for a week then tapered over the subsequent 30 days). Following biopsy results confirming GSA, a Schirmer tear testh was performed. The results were within normal limits, and treatment with isotretinoini (2 mg/kg PO q 24 hr) was initiated. The dog responded very well as the skin and pinnal lesions healed within 2 mo. Treatment with isotretinoin was continued for another 3 mo with a gradual reduction in dose and frequency. No adverse effects were noticed. The dog remained in remission for at least 2 yr after discontinuation of the treatment.
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Case 3
A 6 yr old intact male vizsla presented to the VMTH with a 3 mo history of bilateral purulent and severely painful otitis externa and a 2 mo history of skin lesions. The skin and ear lesions did not respond to treatment after 1 mo of cephalexin (25 mg/kg PO q 12 hr), prednisone (1 mg/kg PO q 24 hr), and ear drops containing ciprofloxacinj. On presentation to the VMTH, the inner ear pinnae were diffusely erythematous with multifocal crusts and erosions of variable sizes (Figure 7). A bilateral aural purulent discharge was noted. The body lesions consisted of multifocal alopecia, papules, nodules, and fine scales over the trunk, head, proximal limbs, and tail (Figure 8). Alopecia, erythema, and swelling were noticed around the eyes. Trichography of the skin lesions showed telogen hair roots covered with thick casts. Smears from the ears revealed neutrophils, cocci, and rods. Skin scrapings were negative for mites. An otoscopic examination performed under general anesthesia showed that the right vertical canal was proliferative, and both vertical canals were ulcerative at their distal ends. Samples for histopathology evaluation were taken from the skin and ear lesions (even though the dog was taking glucocorticoids) because of the lack of response to the medication and the authors’ desire to not postpone any additional treatment. Histopathology from all samples was compatible with the nodular form of sebaceous adenitis. There was a nodular to diffuse infiltrate of epithelioid macrophages mixed with fewer neutrophils centered on the few remaining hair follicles at the level where the sebaceous glands should have been. Ziehl-Neelsen stain was negative for acid-fast organisms (i.e., mycobacteria), and the periodic acid-Schiff stain was negative for fungal structures. CBC and serum biochemistry were normal, and serology for leishmaniasis was negative. After a normal Schirmer tear test, treatment with isotretinoin (2 mg/kg PO q 24 hr) was initiated. Following bacterial culture and susceptibility test results, the dog was also treated with topical ear drops containing polymyxin B and neomycink. After 1 mo of treatment no response of the skin lesions, but good response of the ear lesions was noted. The dog was prescribed a topical propylene glycoll spray (once daily). After 3 mo of treatment complete healing of ear lesions was evident, but no response of skin lesions was noted, and the treatment with isotretinoin was changed to cyclosporin Am (5 mg/kg PO q 24 hr). A marked improvement was achieved after 2 mo, and the treatment was continued on alternate days for another 18 mo with a satisfactory outcome.
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5705
Discussion
GSA is a rare idiopathic disease in dogs that has only been recognized over the last 2 decades.3 All three dogs in this report were vizslas, which are predisposed to GSA, and all three dogs presented with characteristic cutaneous lesions.1,2 Case 2 was older than expected for a first time presentation of GSA; however, Reichler et al. (2001) reported that 30% of 23 Akitas diagnosed histologically with GSA were older dogs.4
In this report the diagnosis of GSA was confirmed histologically in all three cases. The findings were similar to the nodular form of GSA described previously for vizslas by Gross et al. (2005).5 The typical finding in all cases was the diffuse absence of sebaceous glands associated with perifollicular granulomas at the level of the isthmus. Special immunophenotypic markers to differentiate between granulomas of sebaceous adenitis and reactive histiocytosis that attack the follicles and cause destruction of the sebaceous glands were not available for these cases.6,7 Nonetheless, the clinical presentation in this particular breed and the lack of response of skin lesions (all cases) and ear lesions (case 3) to glucocorticoids makes a diagnosis of reactive histiocytosis very unlikely.
All dogs in this report were diagnosed with otitis externa prior to the development of skin lesions. Otitis externa is not a feature of GSA, and the dogs did not present with other signs that could be associated with primary causes or predisposing factors of otitis externa.8 The dogs were not extensively evaluated for other underlying causes for otitis externa, and had presented to the VMTH with severe pinnal lesions after the otitis had already been treated by the referring veterinarians. Had these dogs been presented with signs of ear canal infection or inflammation only, they would have been worked up for the underlying causes of the otitis (i.e., elimination dietary trial). Even had they been presented with a first episode of otitis with the ulcerative pinnal lesions and/or the typical GSA skin lesions, biopsies from the ear and/or skin would have been performed concurrently with the search for the underlying cause and as part of this search. White et al. (1995) reported the occurrence of otitis externa prior to the development of GSA.9 In that report the dog did not have pinnal lesions. In contrast, the pinnal lesions were the most severe and striking clinical signs of the dogs reported herein. Ulcerative pinnal lesions are frequently associated with either immune-mediated diseases such as the pemphigus complex, lupus, an adverse drug reaction, and erythema multiforme or a bacterial infection such as Pseudomonas spp.10,11 Pinnal lesions in all three dogs were similar, and the histopathological findings from ear lesions did not show features of other auto-immune or immune-mediated diseases such as pemphigus, lupus, or erythema multiforme. An adverse drug reaction was also the main differential diagnosis for case 1. Moreover, in the initial diagnosis, the lesions were compatible with sterile granuloma, which responded well to immunosuppressive doses of prednisone. Although not perifollicular, the authors speculated that the granulomas found in the first biopsies in case 1 were also a manifestation of GSA because the dog developed typical cutaneous and histologic lesions shortly afterward. Although P. aeruginosa was isolated in cases 2 and 3, the authors believe that it was not the cause of the ulcerative pinnal lesions because of the unique histologic findings of granulomatous inflammation in these cases and the lack of ulcers along the ear canals. Furthermore, the pinnal lesions responded better to immunosupression and synthetic retinoids than to antibiotics. The response to immunosuppressive dose of prednisone in cases 1 and 2 is not surprising because immune-mediated destruction of the sebaceous glands is one sequel of the putative pathogenesis of the syndrome.1,2 The ear lesions in case 3 did not respond to systemic glucocorticoids, but did resolve with systemic synthetic retinoids.
Two dogs with immune-mediated ulcerative otitis externa responsive to immunosuppressive doses of prednisone were reported by Hendricks et al. (2002).12 One of those dogs was diagnosed histologically with sterile granuloma resembling case 1 in the present report. That dog (reported by Hendricks et al.) also had alopecic lesions on its muzzle, prompting the authors of the current study to question whether the sterile granuloma was also a manifestation of GSA.
The lack of response of skin lesions to synthetic retinoids in case 3 was surprising. It may be explained by either a more pervasive and severe form of the disease or insufficient time had passed before the cyclosporine was prescribed instead of the retinoids.
Conclusion
The cases presented herein were diagnosed with GSA both clinically and histopathologically. These cases are unique in that they differ from the published reports of GSA regarding the severe pinnal ulcerative and granulomatous lesions occurring in all these cases as a part of their skin disease. This observation needs additional evaluation.
Photograph of the ulcerative lesions on the inner side of the right pinna of a 4 yr old female vizsla (case 1) with granulomatous sebaceous adenitis (GSA).
Photograph of the right pinna of a 4 yr old female vizsla (case 1) with GSA. The lesions healed 2 wk after discontinuing a 4 wk course of prednisone.
Histopathology of the alopecic lesions presented in Figure 3 showing GSA. Hematoxylin and eosin stain, original magnification ×100.
Photograph of the left pinna of an 8 yr old female vizsla (case 2) with GSA showing erythema, erosions, and crusts.
Histopathology of the pinnal lesions of Figure 5 showing granulomatous sebaceous adenitis. Original magnification ×200. H&E.
Photograph of the right pinna of a 6 yr old male vizsla (case 3) with GSA showing erosions, ulcerations, and crusts.
Photograph of a 6 yr old male vizsla (case 3) with GSA showing multifocal alopecia and fine scales.
Contributor Notes
