Cutaneous Histiocytosis

What is cutaneous histiocytosis?

Cutaneous histiocytosis (CH) is a benign (non-cancerous) condition in dogs caused by an increased number of immune system cells called histiocytes. Histiocytes help the body recognize and respond to foreign materials, such as pollen and microorganisms. They then travel to nearby lymph nodes and help activate other immune system cells that protect the body.

Cutaneous histiocytosis is one form of a condition called reactive histiocytosis (RH). The other form, systemic histiocytosis (SH), can affect several internal organs. Both forms are uncommon in dogs.

Histiocytes develop from immune system cells called dendritic cells. In CH, the affected cells are a type of dendritic cell called interstitial dendritic cells, which are found in the skin and many other tissues throughout the body.

CH is part of a group of diseases that involve histiocytes and can range from benign to cancerous. In CH, the disease is limited to the skin, the tissues beneath the skin (subcutaneous tissues), and nearby lymph nodes. The affected histiocytes do not show cellular signs of cancer or malignancy.

What are the signs of cutaneous histiocytosis?

CH typically appears as multiple nodules (lumps), both on and beneath the skin. These nodules may occur anywhere on the body and can reach 1.6 inches (4 cm) in diameter. They tend to be painless and not itchy. If they are ulcerated, they may become infected with bacteria. Affected dogs may develop nodules that seem to disappear on their own and later reappear in different locations on the body. They may also cause the dog’s nose to become enlarged, a sign sometimes called “clown nose.”

CH can resemble several other skin conditions and sometimes requires extensive diagnostic testing. CH is limited to the skin, so affected dogs do not develop systemic signs such as fever, weight loss, poor appetite, breathing problems, or digestive upset. If systemic signs are present, the dog may be suffering from systemic histiocytosis or one of the other cancerous versions of histiocytic disease.

What causes cutaneous histiocytosis?

CH is an immune dysfunction, possibly caused by an abnormal immune response triggered by ongoing exposure to substances that stimulate the immune system. Although certain infections can trigger this reaction, the cause of most cases remains unknown. No breed appears more likely to develop this condition than another. CH can occur in dogs of any age and affects males and females equally.

How is cutaneous histiocytosis diagnosed?

Fig. 1: A punch biopsy collects a small sample of skin and underlying tissue for diagnostic testing.

Your veterinarian may suspect this condition during a physical examination, but confirming the diagnosis usually requires microscopic examination of tissue samples. To obtain the appropriate samples, your veterinarian may recommend one or more sampling techniques, including:

• Fine needle aspiration (FNA): Using a small needle and syringe to collect a sample of cells directly from the lump or lesion   
• Punch biopsy: Using a small, circular tool to remove a small piece of skin and the tissue beneath it 
• Surgical removal: Removing a lump or lesion for examination

Cytology is the microscopic examination of cell samples. This method is useful for rapid or preliminary screening and may identify cancerous (malignant) cells when they are present. Cytology alone, however, will not distinguish reactive histiocytosis from other inflammatory reactions.

Histopathology is the microscopic examination of tissue samples that have been specially prepared and stained. Histopathology provides the most accurate diagnosis and can help predict how the lesions are likely to behave over time (their prognosis). Histopathology also rules out the possibility of cancer. Your veterinarian will submit the samples to a specialized laboratory, where a veterinary pathologist will examine them under a microscope. 

The piece of tissue may be a small part of the mass (biopsy) or the whole lump. The whole lump usually provides the most information and may also indicate whether the lesion has been fully removed. However, histopathology of a single lump does not indicate whether there is a systemic disease and to what extent. Combining the information obtained from the biopsy sample along with signs of systemic illness will help differentiate between cutaneous and systemic histiocytosis.

Your veterinarian may also recommend immunophenotyping of the biopsy sample. This test identifies specific markers on the surface of the cells that make up the lump or nodule. While this cannot be used to distinguish between cutaneous and systemic histiocytosis, it can be used to rule out other similar-appearing diseases, including various forms of cancer (e.g., lymphoma).

How is cutaneous histiocytosis treated?

Medical management generally includes an initial treatment phase followed by a long-term phase, during which your veterinarian may gradually reduce medication doses and monitor the dog for recurrence.

For multiple or recurrent CH lesions, immune-modulating drugs are generally the first line of treatment. A variety of drugs have been used, including niacinamide (vitamin B3) combined with tetracycline, prednisone, cyclosporine, and leflunomide. Azathioprine is also sometimes used for more difficult-to-treat cases.

Surgical removal of lumps can be considered for small or solitary lesions, but it does not guarantee new lesions will not develop elsewhere on the body. No single treatment is successful in every case, and your veterinarian may need to try several different medication regimens. Lesions may spontaneously regress, especially during the early stages of the disease, but recurrence is common.

What is the long-term outlook?

Response to treatment is usually good, though long-term therapy is often needed. The time it takes for nodules or lesions to disappear varies widely. Reported treatment times range from 10 to 162 days. Recurrence is always possible, so long-term monitoring and periodic rechecks are recommended.