History
A 10-month-old 28.6-kg (62.9-lb) sexually intact female chocolate Labrador Retriever was referred to the veterinary dermatology service at a veterinary medical teaching hospital for evaluation because of a 2-month history of progressive crusting dermatitis with associated pruritus. The owners described the crusting lesions as resembling tree bark. Skin lesions were progressive, and treatment of the dog for 6 weeks with an elimination diet trial, an ectoparasite control product, and systemic and topical antimicrobial administration was ineffective. Results of examination of skin scraping preparations, fecal flotation testing, and screening for heartworm and tick-borne diseases were negative. Bacterial culture and antimicrobial susceptibility testing of skin lesion specimens were performed and yielded methicillin-resistant Staphylococcus schleiferei. However, skin lesions persisted despite a 4-week course of marbofloxacin (3.5 mg/kg [1.6 mg/lb], PO, q 24 h) selected on the basis of the culture results. Prior to referral, a skin biopsy specimen was obtained from the dog's dorsolateral cervical region and submitted for histologic examination at a commercial laboratory, and the dog was empirically prescribed ketoconazole (10.5 mg/kg [4.8 mg/lb], PO, q 12 h) for suspected dermatophytosis. In addition to anxious behavior, the owners reported that the dog also had moderate to marked lethargy in the 2 weeks prior to evaluation at the hospital.
Clinical and Gross Findings
At the referral evaluation, the dog was bright, alert, and responsive and its heart rate, respiratory rate, and rectal temperature were within reference intervals. In the examination room, the dog was noticeably pruritic; it frequently rubbed its head and face and chewed the skin over the caudal aspect of its dorsum. There were generalized, multifocal to coalescing regions of mild to marked patchy, partial alopecia and multiple plaques of yellow-brown, 0.25- to 1-cm-thick, exophytic crusting that had a prominent irregular surface. Crusting lesions were present in the periocular region, haired areas of the face, dorsal aspect of the cranium, pinnae, dorsolateral and ventral cervical regions, flanks, and pelvic limbs; the right dorsolateral cervical region was most severely affected (Figure 1). On closer inspection, crusts had incorporated hair shafts as a result of coalescing, marked follicular casting. Mild to moderate erythema and moist, erosive dermatitis surrounded the base of several crusts. Microscopic examination of acetate tape impressions from the skin lesions stained with a Romanowsky-type stain revealed neutrophils and intra- and extracellular cocci, consistent with a superficial pyoderma. Bacterial culture and antimicrobial susceptibility testing of a specimen of the crusting lesions on the dorsolateral aspect of the neck were performed and yielded Pseudomonas aeruginosa, Enterobacter cloacae, and methicillin-resistant Staphylococcus pseudintermedius.
Photograph of the right dorsolateral cervical region of a 10-month-old sexually intact female chocolate Labrador Retriever that was referred for evaluation of a 2-month history of a progressive crusting dermatitis with associated pruritus. Notice the well-demarcated partial alopecia in addition to multiple plaques composed of moderate to marked, yellow-brown, thick, exophytic crusting with a pronounced irregular surface. Crusts have incorporated hair shafts as a result of coalescing of marked follicular casting. Mild to moderate erythema and moist, erosive dermatitis surround the bases of some crusts.
Citation: Journal of the American Veterinary Medical Association 257, 4; 10.2460/javma.257.4.387
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
Sections of the skin biopsy specimen obtained by the referring veterinarian underwent histologic examination. The epidermis was characterized by marked acanthosis with spongiosis, dispersed apoptotic keratinocytes with rare lymphocytic exocytosis, and severe parakeratosis. Within the superficial dermis, there was a dense lichenoid infiltrate consisting primarily of plasma cells and lymphocytes with occasional admixed pigment-laden macrophages (Figures 2 and 3). Many hair follicles were characterized by lymphocytic and neutrophilic mural folliculitis with numerous apoptotic keratinocytes (Figure 4). The follicular epithelia were hyperplastic with marked parakeratosis.
Photomicrograph of a section of a skin biopsy specimen from the dog in Figure 1. A dense lichenoid cell infiltrate is abutting the acanthotic epidermis. The infundibula and isthmus of hair follicles contain inflammatory infiltrates. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 257, 4; 10.2460/javma.257.4.387
Photomicrograph of another section of a skin biopsy specimen from the dog in Figure 1. Numerous neutrophils have infiltrated the follicular epithelium and lumen. Numerous lymphocytes and plasma cells form a dense superficial dermal infiltrate. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 257, 4; 10.2460/javma.257.4.387
Photomicrograph of another section of a skin biopsy specimen from the dog in Figure 1. Numerous necrotic or apoptotic keratinocytes are associated with lymphocytes and neutrophils that have infiltrated the hair follicle. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 257, 4; 10.2460/javma.257.4.387
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: severe lichenoid lymphoplasmacytic interface dermatitis with epidermal and follicular apoptosis, lymphocytic exocytosis, and lymphocytic mural folliculitis with parakeratosis consistent with proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts (PLIMFD)1 in a Labrador Retriever.
Comments
Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts is a rare and poorly understood clinical condition that has been reported for 5 Labrador Retrievers to date and requires histologic examination findings for definitive diagnosis.1 The previously described dogs with PLIMFD were all females (4 spayed and 1 sexually intact). The median age at the time of diagnosis was 6 years (range, 2.5 months to 9.5 years). Characteristics of PLIMFD include prominent follicular casting that adheres hair shafts together to form thick, variably sized, and firmly adherent crusts on the haired skin of the perioral and periocular regions, muzzle, chin, head, pinnae, ear canals, neck, ventral aspect of the abdomen, trunk, and limbs. In 2 of the 5 dogs described in the previous report,1 comedones were present in the lesser haired regions of the medial portions of the pinnae, abdomen, and inguinal region. As evident in the dog of the present report, a peripheral rim of erythema that borders crusts and secondary superficial pyoderma are frequently observed.1 In 4 of the 5 dogs described in the previous report,1 pruritus of variable severity was present. Systemic signs of PLIMFD-related illness were uncommon among those dogs; 1 dog had mild lethargy and inappetence.1 Differential diagnoses for PLIMFD include primary seborrhea, vitamin A-responsive dermatosis, zinc-responsive dermatosis, psoriasiform-lichenoid dermatosis, congenital follicular parakeratosis, dermatophytosis, and hyperkeratotic erythema multiforme.1
Histologically, PLIMFD is characterized by moderate to severe, regular to irregular acanthosis of the infundibular follicular epithelium with prominent parakeratotic hyperkeratosis that distends hair follicles and surrounds hair shafts to form follicular casts or comedones. Mild to moderate numbers of apoptotic keratinocytes and frequent lymphocytic satellitosis are present throughout all levels of the epidermis and infundibular follicular epithelium; however, the superficial layers are typically more severely affected. Secondary to follicular parakeratosis, the epidermis may have a papillated surface formed by layered peaks of compact parakeratosis, serous fluid, or serocellular crusts. These layered peaks often adhere to the margins of parakeratotic follicular casts. Interface, perivascular, and interstitial dermal inflammation primarily consisting of lymphocytes, plasma cells, neutrophils, macrophages, and eosinophils have all been described. Pustular crusts, luminal folliculitis, and colonies of gram-positive cocci within crusts were frequently identified in the dogs of the reported case series.1 Histologic features of PLIMFD are similar to those of erythema multiforme, particularly those of the hyperkeratotic variant of erythema multiforme.2 Although both diseases are associated with transepidermal cytotoxic dermatitis, the histologic lesions of PLIMFD are more folliculocentric and feature more superficial apoptosis, less basilar hydropic degeneration, and more marked hyperkeratosis and parakeratosis relative to the lesions of classic erythema multiforme.2
Histologically, PLIMFD also closely resembles feline proliferative and necrotizing otitis externa; both diseases are associated with apoptotic keratinocytes, epidermal hyperplasia, and parakeratosis that preferentially affect the hair follicles.3
Following diagnosis of PLIMFD, the dog of the present report was prescribed cyclosporine (5.24 mg/kg [2.38 mg/lb], PO, q 24 h) and frequent applications of a chlorhexidine-based antimicrobial topical preparation in addition to oral treatment with fluralaner. The latter was prescribed because of the dog's pruritus involving the caudal portion of the dorsum, lack of treatment with a flea preventative, and suspicion for concurrent flea allergy dermatitis. Approximately 95% resolution of all skin lesions was evident at a recheck examination 28 days following the referral evaluation, with only subtle follicular casting remaining on the dorsal cervical region and tips of the pinnae. There was no evidence of pyoderma at this recheck examination. Complete resolution of all skin lesions was reported by the owner 45 days following the referral evaluation, at which time tapering down the dosage of cyclosporine was recommended. Treatment of the dog with cyclosporine was gradually tapered and ceased over a 7.5-month period. The dog had no clinical signs 1 month after discontinuation of the cyclosporine treatment.
Of the 5 dogs with PLIMFD in the previous report,1 1 did not receive treatment. Similar to the outcome for the dog of the present report, 3 of the 5 dogs attained complete remission with cyclosporine monotherapy within 1 to 10 weeks.1 At the time the case series was published, treatment with cyclosporine was discontinued for 2 dogs without clinical relapse for at least 7 to 8 months and 1 dog was receiving 50 mg of cyclosporine once weekly while treatment was being gradually tapered.1 In contrast, 1 of the 5 dogs largely responded to a combination of prednisone, azathioprine, and cyclosporine, albeit without attainment of complete remission.1 In that dog, lesions recurred after all medications were discontinued, and the dog became refractory to subsequent treatment; lesions were noted to have a normal waxing and waning course with or without treatment.1
Although too few cases of PLIMFD have been reported to determine definitive age, sex, and breed predispositions, it is suspected that the development of the disease is influenced by genetic or hormonal factors, given that only female Labrador Retrievers are known to have been affected to date. Furthermore, the response of dogs with PLIMFD to immunomodulatory treatment supports an immune-mediated etiopathogenesis. On the basis of their shared histologic features, PLIMFD and erythema multiforme may be in the same spectrum of disease. However, the striking clinical characteristics, apparent breed predilection, follicular-oriented cytotoxic dermatitis, and marked parakeratosis associated with PLIMFD would appear to define it as a unique clinical disease. Submission of fresh skin biopsy specimens for metagenomic analysis and genetic testing of sera from affected individuals may further elucidate the pathogenesis and genetics of this emerging syndrome. Although the histologic lesions of PLIMFD are readily apparent, a lack of awareness of this rare and poorly understood condition by both clinicians and pathologists may lead to prolonged implementation of inappropriate treatment. The presence of follicular-oriented transepidermal cytotoxic dermatitis and parakeratosis in a Labrador Retriever should prompt consideration for PLIMFD.
Acknowledgments
The authors declare that there were no conflicts of interest.
References
1. Hargis AM, Myers S, Gortel K, et al. Proliferative, lymphocytic, infundibular mural folliculitis and dermatitis with prominent follicular apoptosis and parakeratotic casts in four Labrador Retrievers: preliminary description and response to therapy. Vet Dermatol 2013;24:346–354.
2. Yager JA. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis: a comparative review. Vet Dermatol 2014;25:406–e64.
3. Gross TL, Ihrke PJ, Walder EJ, et al. Necrotizing diseases of the epidermis. In: Skin diseases of the dog and cat: clinical and histopathologic diagnosis. 2nd ed. Oxford, England: Blackwell Scientific Ltd, 2005;79–80.
