Abstract
Introduction
Relapsing polychondritis (RPC) is a rare disease in humans. It is characterised by recurring episodes of inflammation of cartilaginous tissue throughout the body and is considered to be an immune-mediated disease of type II collagen, which is restricted to cartilage (Katz 1993). Antibodies against type II collagen have been demonstrated (Foidart et al 1978), although antibodies against collagen IX, collagen XI and matrilin-1 have also been found in patients with RPC (Buckner et al 2000, Yang et al 1993). There are only 11 cases of feline RPC reported in the veterinary literature (Badoil 1996, Bunge et al 1992, Guaguère et al 1992, Lemmens & Schrauwen 1993, Scott 1987).
The purpose of this article was to describe two additional cases of feline RPC and provide a review of the literature.
Cases
Case 1 (Fig 1)
Siamese cat, 6 years, male castrated. Bilateral deformation of the ears.
A six-year-old, castrated, male, Siamese cat was referred to the Clinic for Companion Animals, University of Bern, Switzerland, because of erythema, swelling, alopecia and crusting of the ears. Swelling of the ears was first observed five weeks prior to referral. At that time, the ears were pruritic and head shaking was noted. One week later, the cat was presented to the referring veterinarian who suspected an allergic reaction. Treatment with prednisolone at a dose of 1.1 mg/kg once daily, administered orally, for two weeks followed by 1.1 mg/kg, every other day for one week was initiated. An ointment containing hydrocortisone was applied topically. Two weeks prior to referral, the head shaking became more frequent, the ear margins started to curl and hair loss on the pinnae was noticed. Full thickness biopsies of the ears had been performed by the referring veterinarian, but the results were not available at the time of referral. According to the owner, the cat had been tested for feline leukemia virus (FeLV) when it was young and the results were negative. Physical examination revealed erythematous, swollen, hairless and slightly painful pinnae on both sides. The pinnae were crusty. Otherwise the cat was normal. A complete blood count revealed neutrophilia with a left shift (segmented neutrophils 14 600/μl, bands 340/μl) and lymphopenia (1190/μl). A biochemical profile revealed hyperglobulinemia with 58.1 g/l (reference range 26–38 g/l). Alanine aminotransferase was slightly increased at 25 IU/l (reference range up to 23 IU/l). ELISA tests (IDEXX, Maine, USA) for FeLV and feline immunodeficiency virus (FIV) were negative. A skin scraping revealed no parasites or fungal elements. There was degeneration of the cartilage, which had lost its basophilia when stained with hematoxylin and eosin. The pinnal cartilage was wrinkled rather than a normal straight band. The cartilage was surrounded by an inflammatory infiltrate, which consisted of densely packed lymphocytes and a few multi-nuclear giant cells. This infiltrate invaded the cartilage in several areas. There was severe perichondrial fibrosis. The dermis had moderate perivascular inflammation with infiltration of lymphocytes and neutrophils (Fig 2). Because there was no improvement after another treatment with prednisolone at a dose of 1.1 mg/kg daily for ten days, the referring veterinarian amputated both ears. Five years later, the cat was still healthy.
Case 1, ear. Degenerated cartilage with perichondrial lymphocytic infiltration and fibrosis. Lymphocytes invade the cartilage tissue. H&E stain, original magnification 250 x.
Case 2
A 1.5-year-old, female, domestic shorthair cat was referred to the Clinic for Companion Animals, University of Bern, Switzerland, because of bilateral deformation of the pinnae, which had started approximately two months prior to referral. Initial symptoms included erythema and mild pruritus of both ears. The cat was treated by the referring veterinarian with a topical medication containing neomycin, lindane and nystatin. Concurrent lameness of the left hindlimb was observed. No trauma was reported. Tests for FeLV and FIV, performed when the cat was four months old, were negative. At eight months of age, the cat had given birth to one dead and two ‘fading kittens’. On physical examination, there was bilateral aural erythema, and the right pinna was thickened and slightly painful. Auscultation of the heart revealed a grade five systolic plateau heart murmur with maximal intensity over the left heart base. The left stifle joint was thickened but not painful, and the left patella could be luxated. A complete blood count was unremarkable. A FeLV ELISA-test (IDEXX, Maine, USA) was positive. Radiographs of the thorax revealed cardiomegaly, and a joint distention and osteophytes consistent with degenerative changes were seen on a lateral radiograph of the left stifle. Results of electrocardiography indicated left ventricular hypertrophy with a R wave of 1.5 mV in lead two. Echocardiography showed left ventricular dilatation with normal ventricular contractility. The left atrium was slightly enlarged. There was atypical thickening of the chordae tendineae chordis, and the aortic valves were thickened, which resulted in mild turbulence of blood flow. Mild mitral regurgitation was observed, although it was considered to be of minor importance. Based on these results, congenital heart disease with mitral dysplasia was suspected. Biopsy samples of both pinnae were collected and revealed degeneration of the cartilage, which had lost its basophilia when stained with hematoxylin and eosin. The pinnal cartilage was wrinkled rather than a normal straight band. The cartilage was surrounded by an inflammatory infiltrate, which consisted of densely packed lymphocytes and a few multinuclear giant cells.
This infiltrate invaded the cartilage in several areas. The perichondrial region was oedematous. There is also a moderate perichondrial infiltration with neutrophils. The dermis had moderate perivascular inflammation with infiltration of lymphocytes and neutrophils. Unfortunately further follow-up was refused by the owner. Six months later, the cat was euthanatised by the referring veterinarian because of severe dyspnoea. Pulmonary oedema was suspected. A postmortem examination was not performed.
Discussion
To our knowledge, there are only 11 cases of feline relapsing polychondritis (RPC) reported in the literature. The signalement and main clinical findings are summarised in Table 1. Feline relapsing polychondritis is a disease of predominantly young to middle aged cats (median, 3 years), although the age of onset ranges from 1.5 to 14.5 years. There is no sex predilection for feline RPC. With respect to age, breed and gender, our two cases were similar to those in the veterinary literature. In comparison, in 337 human patients with RPC, the average age of onset was 47 years (Trentham & Le 1998), and the female to male ratio in 66 patients was 3:1. Other studies of human RPC reported an equal distribution of males and females (Pearson et al 1960; McAdamn et al 1976, Michet et al 1986).
Summary of data from cats with feline relapsing polychondritis
NR: not reported; DSH: domestic short-hair; MN: male neutered, FS: female spayed; F: female; PRED: prednisolone, FeLV: feline leukemia virus; FIV: feline immunodeficiency virus.
In humans, RPC is characterised by recurrent inflammation of cartilaginous tissue. All types of cartilage may be involved. Proteoglycan-rich structures such as the eye, the heart, blood vessels and the inner ear may also be inflamed (Trentham & Le 1998). In all cats with feline RPC, the ears were affected and the condition in cats was even renamed auricular chondritis (Scott et al 2001). Auricular chondritis is also the most common finding in humans (Trentham & Le 1998). However the clinical findings of case 2, similar to those described by Bunge et al (1992) raise suspicion of involvement of additional cartilaginous tissue to the ear as in people.
Case 2 had radiographic evidence of degenerative changes in the left stifle joint. Unfortunately no further diagnostic evaluation of this joint was performed. Bunge et al (1992) performed joint taps in the cat they describe. The cytology of the fluid was normal. In a summary of three large case studies of humans with RPC, articular involvement was found to be the second most common clinical finding (Trentham & Le 1998). In some cases, arthritis is the first clinical sign observed in patients with RPC (Günaydin et al 1998). Arthritis in men is usually nonerosive in RPC in accordance to the diagnostic criteria first established by McAdam et al (1976). No secondary degenerative changes occurred in four patients with a mean follow up of 4.4 years (Booth et al 1989). Case 2 is the first cat with feline RPC and articular changes. If these changes are secondary to the patella-luxation or to a chronic inflammatory process remains unclear. Histological confirmation would have been needed. However, the degenerative changes appeared too severe for just a patellar luxation in a young cat.
The cat described by Bunge et al (1992) had bilateral opacification of the cornea, consistent with ocular inflammation and keratitis. The histological results of previously taken biopsy samples of the cornea were inconclusive and not further described. Ocular inflammation is a common finding in humans with RPC and is an initial symptom in 14 to 24% of cases (Trentham & Le 1998). Ocular signs vary widely and the cornea might show peripheral thinning and pannus, peripheral infiltrates or nonspecific changes (Isaak et al 1986). Bunge et al (1992) described the ocular lesions in their cat as compatible with a diagnosis of feline RPC. However other causes for the ocular lesions are possible.
In case 2 and the case reported by Bunge et al. (1992), there were cardiac abnormalities and valvular disease was suspected. In a review of the human literature, Arkin & Masi (1975) reported involvement of the heart valves in 9% of patients with RPC; aortic insufficiency was the most common abnormality. In a review by McAdam et al (1976), aortic insufficiency occurred in 5.6% of the cases and mitral insufficiency in 3.1%. However no histological examinations were performed in the two cats and other causes of the heart conditions are well possible.
Case 2 and the cat reported by Bunge et al. (1992) had changes in organs commonly involved in human RPC and the question remains if the term polychondritis instead of chondritis may be appropriate, although this has been questioned by Badoil (1996) and Scott et al (2001).
The histological lesions observed in biopsy samples of the ears were similar in all cases in the literature. There was inflammation, degeneration, necrosis and loss of basophilic staining of the matrix of the ear cartilage. As in humans the inflammatory infiltrates consisted of mono-nuclear and polymorphonuclear cells. Direct immunfluorescence staining of the specimens for immune complexes was performed in two cases and was negative (Bunge et al 1992, Guaguère et al 1992). According to Trentham & Le (1998), there are no histological changes that are pathognomonic for relapsing polychondtritis in people. Specimens of inflamed cartilage may show distinctive features including loss of basophilic staining of cartilage matrix, perichondral inflammation, fibrocyte and capillary endothelial cell proliferation, perivascular infiltration of mono-nuclear and polymorphonuclear cells and vacuolated and necrotic chondrocytes. The histological changes observed in feline RPC are similar.
Fever or hyperthermia was reported in two cats (Guaguère et al 1992, Lemmens & Schrauwen 1993) and is also common in humans with RPC, occurring in up to 44% of patients (Luthra 1998).
An association between RPC and FeLV and FIV has been postulated (Guaguère et al 1992, Scott et al 1995). However, after reviewing the literature, there does not appear to be a definite association between RPC and FeLV and FIV because the majority of cats tested were negative for both viruses (Table 1).
Over 30% of human patients with RPC suffer from an existing autoimmune or hematologic disease (Luthra, 1998). Systemic lupus erythematosus (SLE) is associated with 1.25% of RPC cases in humans (Miyaska 1998). This association in human medicine may have been the reason why several cats were tested for antinuclear antibodies (ANA). Two of four cats tested had positive titers for ANA (Guaguère et al 1992, Badoil 1996). However, SLE was unlikely in these two cats because there were no other clinical signs. Low titers for ANA are not uncommon in normal cats and in cats with FIV (Pedersen et al 2000), for which one of the two cats tested positive.
Three cats reported in the literature were not treated (Scott 1987, Badoil 1996). Treatments provided to the other cats is listed in Table 1. There are no reports of controlled therapeutic trials in the treatment of human RPC. A variety of drugs have been used. Corticosteroids reliably lead to resolution of chondritis (Trentham & Le 1998). In contrast in cats with RPC, various dosages of glucocorticoids were not effective. However, dapsone at a dose of 1 mg/kg/day, administered orally, appeared to result in some clinical improvement but side-effects were observed in one of four cats. It is interesting to note that some of the cats improved without treatment. Thus, the role of treatment in the course of feline RPC is not clear. Dapsone has also been used with success in human RPC (Barranco et al 1976, Martin et al 1976). The proposed mechanism of action of dapsone is lysosomal enzyme inhibition (Barranco et al 1976). Other authors reported treatment with dapsone to be disappointing (Katz 1993).
Most people with RPC develop some degree of disability during the later stages of the disease. The reported survival rates range from 55% at 10 years post-diagnosis to 94% at 8 years (Michet et al 1986, Trentham & Le 1998). The major cause of death in humans is airway-related; pneumonia and collapse of airways are very common (Pearson et al 1960, Dolan et al 1966, McAdamn et al 1976, Michet et al 1986, Trentham & Le 1998). Because follow-up evaluations were not performed in most of the cats with RPC reported in the literature, the prognosis for this feline disease is uncertain. Case 1 of this report remained healthy for at least five years after referral, and three cats reported in the literature were healthy for more than one year. It is not known what caused the dyspnoea in case 2, which led to euthanasia of the cat. No relapsing nature of the disease has been found in all the reported cats but this has to be seen in the light of a short follow up in only few cases. In conclusion feline RPC is a rare disease in cats. As the findings in cats appear very similar to those in human RPC it might still be justified to call the condition feline RPC.