Successful control of disseminated follicular cysts in a dog with low dose isotretinoin

Abstract

A case of disseminated cysts in a dog is described. Histopathological examination revealed the presence of follicular infundibular cysts, which were treated with isotretinoin at a dose of 2 mg/kg body weight (BW), q24h for 1 week, followed by a dose of 1 mg/kg BW for 3 months. Symptoms resolved after this course of treatment.

Follicular cysts are common non-cancerous tumors in dogs and cats (1). The contents of the cysts consist mostly of sebum, keratin, or hair (2). Follicular cysts can be categorized into infundibular cysts, isthmus-catagen cysts, metrical cysts, and mixed cysts (including panfollicular cysts from all parts of the follicle) (3). The etiology of follicular cysts is unknown. It is suspected that they may have a genetic or congenital basis, or they may be a consequence of injury. Trauma can induce plugging or narrowing of follicular ostia, causing retention of follicular contents. The retention of follicular contents causes dilation and, eventually, formation of follicular cysts. Other factors, such as predisposition for follicular hyperkeratosis, may also promote cyst formation in the dog. Follicular cysts usually form single tumors, but some cases of disseminated cysts have also been reported (2). This form of the disease has been reported in dogs, alpacas, sheep, and, in few cases, in cats and horses (1,4–7). Disseminated forms of the disease involve presence of more than 20 cysts in various parts of the body and are diagnosed rarely. Follicular cysts are usually benign, but may evolve into squamous cell carcinomas (8).

Case description

A case of disseminated cysts was diagnosed in a 7-year-old male American Staffordshire terrier dog. At age 5 y, nodules began to appear in the deep dermis on the legs, sides of the thorax, the back/dorsum, and the tail. In the owner’s opinion, there were hundreds of small nodules. The disease had not been diagnosed before a consultation at the Veterinary Clinic at the University of Life Sciences. The animal had been treated with antibiotics [amoxicillin with clavulanic acid (Synulox; Zoetis, Warszawa, Poland), 25 mg/kg body weight (BW), PO, q12h for 5 wk, cephalexin (Kefavet; Orion Corporation, Esppo, Poland), 22 mg/kg BW, PO, q12h, for 4 wk and enrofloxacin (Enroxil; Krka, d.d., Novo mesto, Poland), 5 mg/kg BW, PO, q24h for 3 wk], glucocorticoids [prednisone (Encorton; Pabianickie Zakłady Farmaceutyczne Polfa, Pabianice, Poland), 1 mg/kg BW for 2 wk, dexamethasone (Pabi-Dexamethason; Pabianickie Zakłady Farmaceutyczne Polfa), 0.1 mg/kg BW for 10 d] and shampoos (Malseb; Dechra Veterinary Products, Uldum, Poland and Sebolytic; Virbac, Warszawa, Poland), without any substantial improvement in the dog’s clinical condition.

During the consultation, extensive alopecia and hair thinning were observed on the limbs (especially on the hind limbs), the dorsum, the tail and the sides of the thorax (Figures 1, 2). Also, in the same body region, there were numerous (200 to 300) nodules in the dermis that were 3- to 4-mm in diameter. Fistulae discharging blood and pus were also observed. The animal had moderate pruritus.

Figure 1.

Numerous areas with alopecia and nodules on limbs and sides of the dog’s body.

Figure 2.

Close-up of rear limb showing alopecia and numerous nodules.

The results of a complete blood (cell) count (CBC), serum biochemistry, and tests for free thyroxine (T4), total T4 and thyroid stimulating hormone (TSH) were all within the reference ranges. Skin scrapings were used to rule out demodicosis. The cytological examination of pus revealed numerous degenerated neutrophils, single macrophages, and keratin accumulation. Only keratin accumulation was found in the cytological examination of material from non-inflammatory cysts collected by fine-needle aspiration. Staphylococcus pseudintermedius susceptible to a wide range of antimicrobials was found on bacterial culture. After sedation with detomidine (Dexdomitor; Orion Corporation) and local anaesthesia with 1% lignocaine (Lignocain 1%; Polfa Warszawa, Poland), a 5-mm punch biopsy specimen was collected for histopathological examination. Samples were taken from 3 areas of the body: thorax, right hind limb, dorsum. The histopathological examination of samples stained with hematoxylin and eosin (H&E) revealed the presence of follicular cysts (Figure 3). The cyst wall was thin and made of a multilayer epithelium with a granular layer and a tendency to hyperkeratosis. In the lumen of the cyst, extensive keratin deposits were visible as concentrically arranged thin plaques. Based on these histological features, the cysts were classified as infundibular cysts. Infundibular cysts were observed in all histopathological samples.

Figure 3.

Follicular cyst filled with amorphous material. Stratum granulosum is present, indicating an infundibular cyst. H&E, 400×.

After diagnosing that the dog had disseminated follicular cysts, treatment began, using isotretinoin (Aknenormin; Almirall Hermal GmbH, Reinbek, Germany) at an initial dose of 2 mg/kg BW, PO, q24h. At the same time, antibiotic treatment (amoxicillin with clavulanic acid, Synulox; Zoetis), 25 mg/kg BW, PO, q12h, was used to reduce bacterial complication. The starting dose of isotretinoin was used for 1 wk. In the following week, vomiting was observed and the dose of isotretinoin was reduced to 1 mg/kg BW q24h, PO. After reduction of the dose of isotretinoin vomiting stopped. In the second month of treatment the largest cysts began to shrink, the number of nodules decreased by half and there were no new cysts. Antibiotics were stopped in the second month of therapy but isotretinoin therapy was continued for an additional 2 mo. In the second month of therapy we noted only about 40 to 50 nodules. In the third month of treatment there were only about 10 small cysts on the hind limbs and tail (Figure 4).

Figure 4.

Appearance of the dog after 6 months of treatment. There was no alopecia and there were no nodules.

Discussion

Many differential diagnoses need to be considered in cases of single or multiple dermal or subcutaneous nodules. Abscesses, cysts, papillomas, infectious diseases, neoplasias, and immunemediated diseases should also be considered.

The case reported here is a rare form of disseminated follicular cysts. We speculate that follicular cysts were a primary developmental abnormality in this case, because formation of cysts and nodules was first observed before development of deep pyoderma. In such cases, use of the term disseminated follicular cysts or multiple follicular cysts is proposed. In the literature both terms can be found, but it seems reasonable that the name multiple cysts should be used in cases in which multiple cysts are located on only one part of the body and disseminated cysts in cases in which cysts are noted on several body regions. In dogs, this form of the disease has been reported for infundibular cysts, and in horses and llamas, other types of disseminated cysts (isthmus-catagen or hybrid) have been reported as well (2,4,5). A case with numerous (about 100) follicular cysts (infundibular) located in the perianal area of a dog has been described (7).

The treatment of follicular cysts usually requires surgical dissection, but this method is not possible in cases of numerous cysts. Laser therapy has been successfully used in canine interdigital palmar and plantar comedones and follicular cysts (9). Laser surgery is a good treatment option in addition to traditional surgery. As far as pharmacological treatment is concerned, isotretinoin is used at a dose of 1.5 to 3 mg/kg BW, q24h, PO, which, in some cases, blocks the development of the disease (2). The effect of isotretinoin is based on significantly reduced keratinization, although the exact mechanism of this process is not known. In one case, treatment with vitamin A (466 IU/kg BW per day) was reported to stop progression of the disease (1). In horses with epidermal inclusion cysts, intralesional injections of neutral-buffered 10% formalin have been successfully used, but this method is restricted to cases in which cysts are large and low in numbers (10).

The side effects of retinoids are well-documented in humans (11). Most commonly these include keratoconjunctivitis sicca, cheilitis, xerosis, pruritus, and facial dermatitis, thinning and loss of hair, palmo-plantar scaling, sight alteration, high liver enzyme serum levels, bone pain, skeletal abnormalities, and myopathies. Retinoids have teratogenic effects as well. In dogs, side effects are rare. The most frequent are elevation of serum liver enzymes and serum lipids, and keratoconjunctivits sicca (12). Monitoring of liver enzymes, lipids, and tear production is recommended during retinoid treatment.

In the present case the use of retinoids successfully blocked the development of the disease despite using lower than recommended doses. CVJ