Signalment:  

12 yr-old, male, castrated, West Highland White Terrier, (Canis familiaris), dog.Starting in November 2006, the patient developed periodic episodes of coughing fits (dry, hacking, non-productive). Coughing episodes increased over several weeks. In January 2007, the owners noticed the dog had increased respiratory rate and effort. The dog was started on Clavamox-� but the respiratory problems continued with no improvement. Two days prior to admission (1/9/2007), the owner reported that the dog had respiratory distress with an abdominal component, and lethargy.

On presentation, the patient's mucus membranes were cyanotic, pulse = 162, respiratory rate = 60 - 80, and crackles were ausculted bilaterally. No murmur was heard, but heart sounds were difficult to hear over the crackles. The dog was placed in an oxygen cage and heart rate decreased to 120 and mucus membranes were pink. Jugular pulses were increased. Cough could not be elicited on tracheal palpation. Respiratory rate and effort remained increased while in the oxygen cage.

Only one lateral thoracic radiograph was able to be obtained before the dog became very distressed and was placed back in the oxygen cage. The radiograph showed mild to moderate right sided cardiomegally and diffuse interstitial to alveolar lung pattern, more pronounced dorsocaudally.

A brief echocardiogram, with the dog standing in the oxygen cage, revealed extremely enlarged right ventricle with thickened free wall.

Physical exam, radiographic and echocardiographic studies were all consistent with pulmonary fibrosis and pulmonary hypertension.

Gross Description:  

The lungs did not collapse when negative pressure was released. All lung lobes were diffusely dark pink, firm, and were meaty and dark red on cut section. The capsular surfaces of both kidneys were pitted and irregular with a tightly adhered capsule and multifocal <1mm diameter cortical cysts. There were bilateral mature cataracts.

Histopathologic Description:

Lungs - There is diffuse thickening of the alveolar septae with fibroblasts and homogenous eosinophilic fibrillar material (collagen). Occasionally, sepatae are dramatically thickened up to 5 times. Partially or completely filling the alveolae are numerous macrophages with light pink vacuolated cytoplasm with occasional multinucleate cells. There is marked type II pneumocyte hyperplasia. Occasionally there is light purple mineralized material within the alveoli. Some sections contain a thick trabecula of dense collagen lined by hypertrophied type II pneumocytes.

Masson's trichrome stain shows moderate diffuse staining of the alveolar septae. There is multifocal to diffuse staining of cells within the alveolar septae for smooth muscle actin (myofibroblasts). There is negative staining for Collagen type I. (Reliable immunostains for collagen III, and IV were unavailable). Many intraalveolar cells stain positive for cytokeratin (pneumocytes).

Morphologic Diagnosis:  

Lung - Marked, diffuse, chronic, interstitial fibrosis with type II pneumocyte hyperplasia.

Lab Results:  

Complete blood count and chemistry profile were fairly unremarkable with the following abnormalities:

Leukocytosis (23.5000 x103/ul; reference range 4.900 - 16.900 x103/ul) with mature neutrophilia (19.270 x103/ul; reference range 2.800 - 11.500 x103/ul). No abnormalities were noted on the differential. Alkaline Phosphatase was markedly increased (1484 U/L; reference range 12 - 121 U/L)

Condition:  

Idiopathic pulmonary fibrosis

Contributor Comment:  

Idiopathic interstitial lung disease is a complicated and poorly understood disease process that, in the dog, has been described mostly in the terrier breeds with the West Highland White terrier having the highest incidence¹. The clinical signs consist of coughing, dyspnea, exercise intolerance, and cyanosis. The signs develop slowly, and affected dogs deteriorate progressively over months2. Inspiratory crackles are a common physical exam finding and the main radiographic changes consist of mild to severe increased interstitial pattern and right sided cardiomegally. Bronchoscopic findings are often normal or show mild airway mucoid reaction². Usually there are no hematologic or serum biochemical abnormalities.

Histopathologic findings consistently show generalized thickening of the interstitium by variable amounts of eosinophilic extracellular matrix. The process can range from diffuse to multifocal or regional. The most severe cases have multifocal areas of type II pneumocyte hyperplasia. There are often variable amounts of inflammatory cells (lymphocytes, plasma cells, macrophages.) Masson's trichrome stains the extracellular matrix expanding the alveolar septae as collagen¹. Immunohistochemistry reveals that there can be a mixture of type I and type III collagen depending on the severity and chronicity of the disease¹. Ultrastructurally, the extracellular matrix consists of numerous bundles of electron dense fibrils aligned parallel to one another. Individual fibrils have even spaced band periodicities (collagen)¹.

Differentials for idiopathic interstitial lung disease include, chronic bronchiolitis, neoplasia, and infectious diseases⁵. Idiopathic interstitial lung disease is of unknown etiology. Infectious processes, drug reactions, exposure to toxins or dust, and connective tissue disorders have been hypothesized as potential etiologies. Diagnosis, treatment, and determining an underlying etiology is difficult because by the time clinical signs are seen, there is usually irreversible loss of pulmonary function (fibrosis), and the inciting cause may no longer be present. 

In human medicine there are a group of idiopathic pneumonias with similar features of shortness of breath, radiographic evidence of diffuse pulmonary infiltrates and varying degrees of inflammation, and fibrosis. The terminology in human medicine for these diseases has changed. Previously, many form of idiopathic interstitial pneumonia were termed "idiopathic pulmonary fibrosis", which is now reserved for a specific type also known as "usual interstitial pneumonia" or "cryptogenic pulmonary fibrosis"³. This diseasae in humans has some similarities as the disease seen in West highland White terriers but technically the same. Other types of idiopathic interstitial pneumonias besides usual interstitial pneumonia, include, acute interstitial pneumonia, non-specific interstitial pneumonia, cryptogenic organizing pneumonia, and desquamative interstitial pneumonia-respiratory bronchiolitis interstitial lung disease³.

JPC Diagnosis:  

Lung: Fibrosis, interstitial, diffuse, marked, with type II pneumocyte hyperplasia, and intraalveolar macrophages and multinucleated giant cells, West Highland White Terrier, canine.

Conference Comment:  

The contributor provides an excellent review of interstitial lung disease of the West Highland White Terrier. Idiopathic Pulmonary Fibrosis also occurs in middle-age to older cats. Adult horses develop nodules of interstitial pulmonary fibrosis (Equine multinodular pulmonary fibrosis).

Additional causes of pulmonary fibrosis were discussed. Anything that damages type I pneumocytes or alveolar endothelium may lead to pulmonary fibrosis. Causes of alveolar damage include irradiation, septicemia, thermal injury, vomit aspiration, toxic gases (e.g., oxygen toxicity) and toxins (e.g., paraquat).

Other conditions with an increased prevalence in West Highland White Terriers include craniomandibular osteopathy, polycystic liver and kidney disease, hyperplastic dermatosis, and chronic hepatitis and cirrhosis.

References:

1 Norris AJ, Naydan DK, Wilson DW: Interstitial lung disease in West Highland White Terriers. Vet Pathol 42:35-41, 2005
2 Corcoran BM, Cobb M, Martin MWS, Dukes-McEwan J, French A, Fuentes VL: Chronic pulmonary disease in West Highland White Terriers. Vet Rec 144:611-616, 1999
3. Gross TJ, Hunninghake GW: Idiopathic pulmonary fibrosis. N Engl J Med 345:517- 525, 2001
4. Lobetti RG, Milner R, Lane E: Chronic idiopathic pulmonary fibrosis in five dogs. J Am Anim Hosp Assoc 37:119-127, 2001
5. Webb JA, Armstrong J: Chronic idiopathic pulmonary fibrosis in a West Highland white terrier. Can Vet J 43:703-705, 2002

A virtual slide is not available for this case.

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