Frequently Asked Questions - Canine Histiocytosis
Q1. My dog has "histio", is this disease invariably fatal?
"Histio" is a term loosely coined by dog breeders and other members of the public; the term implies there is only one form of histiocytic disease that afflicts dogs. However there are 2 broad groups of diseases (and multiple diseases) that involve proliferation of histiocytes. The first group, which includes cutaneous histiocytosis (CH) and systemic histiocytosis (SH), consists of reactive (ie inflammatory) diseases in which a disorder of immune system regulation is suspected. Dogs afflicted with these diseases often require systemic immunosuppressive therapy to control their symptoms, especially late in the course of disease. Early on, lesions of CH and SH may resolve spontaneously presumably because the imbalance in the immune system has corrected itself and/or the initiating agent/antigen has been eliminated. The second group of histiocytic diseases consists of neoplastic diseases of histiocytes, which includes histiocytoma and the histiocytic sarcoma complex (HS). Histiocytoma is largely a benign disease which will resolve spontaneously in most, but not all instances. Histiocytic sarcoma complex consists of the malignant histiocytic neoplasms. It occurs as solitary HS (better prognosis if treated early), and disseminated HS - this was historically referred to as malignant histiocytosis (MH). Disseminated HS has a poor prognosis, since by definition, the disease process involves a number of organs when first discovered. Since chemotherapy (using many different protocols) has not been successful in any of the past cases, it is common for dogs afflicted with disseminated forms of HS to succumb to their disease in a just a few weeks to several months. So the short answer to your question is NO but I would immediately ask you what form of histiocytic disease does your dog have (based on the above definitions). Without accurate diagnosis it is not possible to give a prognosis.
Q2. What clinical signs would indicate that my dog may have a histiocytic disease?
This depends on the type of histiocytic disease - reactive or neoplastic. Reactive histiocytic disease almost invariably involves the skin where it is associated with nodules that form in the dermis and subcutis, These nodules are most commonly seen on the face (muzzle, nose and eyelids), scrotum, and trunk, but can occur in any location. The nodules may ulcerate and ooze. This pattern is typical of cutaneous and systemic histiocytosis (CH and SH). In SH, there will be some additional evidence of spread beyond the skin. This is most easily recognized when there is involvement of the ocular and nasal mucous membranes. Reddening and swelling of the conjunctiva, corneal edema, and corneal vascularization may be seen. Nasal discharge and snoring respiration, which indicate nasal mucosal infiltration by histiocytes, may also be seen. Dogs with CH are often bright, alert and outwardly unaffected by their disease. In contrast, dogs with SH, are often anorexic and lose weight; they may be clinically depressed as well. This reflects the more aggressive and widespread tissue involvement in SH.
Neoplastic histiocytic disease (especially the histiocytic sarcoma complex - HS) may involve the skin or subcutaneous tissues resulting in mass formation (masses are bigger than nodules). These masses are commonly on limbs, but they can occur in almost any surface location. In one form of histiocytic sarcoma, periarticular/articular HS, the masses can encircle joints and may be associated with lameness. In other instances, HS affects internal organs and spares the skin and subcutaneous tissues (this is an important distinction). Dogs with this latter involvement usually exhibit vague clinical signs such as lethargy, anorexia and weight loss. Anemia is not a consistent finding unless the histiocytes manifest aggression toward red blood cells - this is seen in the hemophagocytic HS - a primary disease of spleen and bone marrow. Other clinical signs depend on location of the neoplastic histiocytes. Primary sites include spleen, lung and bone marrow. Liver is often affected after metastasis of a splenic tumor(s), since the splenic vein drains into the portal vein of the liver. Primary splenic disease can go undetected for some time unless the neoplastic histiocytes announce their presence in some noticeable way (eg hemophagocytosis and resulting anemia). Pulmonary HS can lead to respiratory difficulty due to destruction of lung tissue - the lung has a considerable functional reserve, so lesions can be large and usually have spread to the hilar lymph nodes by the time respiratory difficulty has appeared. Hilar lymph node metastasis can compromise the trachea, which is nearby, and may cause further respiratory distress. Primary HS in bone marrow is usually silent unless the histiocytes are hemophagocytic, or if the site is strategically located - e.g. a vertebral body lesion can destroy the bone and compress the spinal cord. Primary HS in brain does occur and can result in paresis, paralysis and seizure activity depending on location. Spread beyond the brain has only been seen in a single case (Moore, unpublished data).
Q3. What are the treatment options for canine histiocytic diseases and where can my vet find information on this topic?
Reactive histiocytic disease - cutaneous and systemic histiocytosis - treatment when indicated usually begins with corticosteroids ($), but many dogs do not respond (only about 10% of our cases). More potent systemic immunosuppression is then required. We have used Cyclosporin A (Atopica $$$) or Leflunomide (Arava $$$) by oral administration. These drugs are reasonably well tolerated, but they are expensive. We find that Cyclosporin A eyedrops (Optimmune) must often be used in conjunction with systemic therapy to control the eye lesions. Information on the use of these and other immunosuppressive drugs is available in Current Veterinary Therapy XIV, WB Saunders, 2009.
Neoplastic histiocytic disease - Cutaneous histiocytoma is largely benign and with rare exceptions, surgical excision is usually curative. Localized histiocytic sarcoma can be cured by excision prior to metastasis. Once metastatic disease has occurred in localized histiocytic sarcoma, OR in instances of disseminated histiocytic sarcoma surgical treatment is no longer an option. Chemotherapy has not been successful in management of histiocytic sarcoma complex. Despite the use of many different protocols, response has at best been brief.
Q4. My dog has just been diagnosed with cutaneous histiocytosis - he has several nodular skin lesions on the trunk that do not appear to bother him. Do I need to start immediately with immuno suppressive drug therapy?
Immunosuppressive therapy for aggressive reactive histiocytic disease is a life long prospect in many instances. There are untoward consequences of such therapy. You and your vet will have to weigh the benefits of treatment against the negative aspects of treatment, which include an increased risk of serious infection and the high cost of the most efficaceous drugs. Initially reactive histiocytic disease can often spontaneously resolve; in fact dogs may have several such episodes punctuated by disease free periods of many months. Therapy is necessary when the disease is continuously active and is unlikely to regress OR if lesions involve critical or sensitive tissues such as those of the orbit and nasal mucosa.
Q5. My Bernese Mountain Dog has systemic histiocytosis - he has ulcerated skin lesions. I have young children who love to hug him. Is there any risk of them catching this disease?
Despite the unsightly lesions, there is no evidence that systemic histiocytosis is contagious to other dogs or humans. Your dog's lesions are due to an imbalance in his immune system.
Q6. My Bernese Mountain Dog has developed systemic histiocytosis. I have heard that this disease is invariably fatal. Should I have him put down now so that he does not suffer unduly?
This is a common misconception. Many in the past have lumped histiocytic sarcoma and reactive forms of histiocytosis together despite a major difference in outcome. Systemic histiocytosis is a treatable disease, and even if left untreated it would not normally lead to rapid organ failure and death, which is commonly seen in HS. Reactive histiocytoses are actually quite uncommon in Bernese mountain dogs and occur in younger dogs than do HSs, so there are few cases out there to follow. Hence the existence (and incidence) of conversion of reactive histiocytosis to HS is still not known
Q7. My Bernese Mountain Dog is only 8 months old and he already has had a histiocytoma removed from his lip. Does this mean he will invariably get one of the other bad forms of histiocytosis?
There is no known connection between the development of histiocytomas and other histiocytic diseases in this breed. Histiocytoma occurs sporadically in ALL breeds and is the most common neoplasm in dogs. The peak incidence is in the 2-3 year age group. Histiocytomas exhibit Langerhans cell differentiation, while other histiocytic diseases are largely derived from interstitial dendritic cells (DC). It appears that the defects that lead to development of HS are more highly expressed in interstitial DC populations.
Q8. Why can't we just find the defective gene in familial histiocytic diseases and breed unaffected dogs to eliminate these diseases?
Both forms of familial histiocytic disease (reactive and neoplastic) likely are polygenic disorders. That is there are multiple genetic defects involved in the development of these diseases. It is likely that combinations of abnormal genes lead to disease. Hence, even outwardly normal individuals could carry altered genes that are only manifest when they coexist with other critical altered genes necessary for disease development. Hence, 2 totally unaffected parents can produce dogs with high susceptibility to disease development if the right mix of genes is present. Clearly this is a far more complex situation than simple single recessive or dominant genetic traits. The existence of multiple silent genetic abnormalities is difficult to exclude on an individual basis until all genes contributing to development of histiocytic disease have been identified. Identification of disease susceptibility genes and gene mapping efforts are currently not very advanced in the canine genome. So there are very few identified candidate genes to investigate.
Q9. Are Bernese Mountain Dogs the only breed affected by histiocytic diseases?
Bernese Mountain Dogs have a staggering incidence of histiocytic diseases, especially the the neoplastic histiocytic diseases - the histiocytic sarcoma complex, and to a lesser extent the reactive histiocytic diseases - cutaneous and systemic histiocytosis. These diseases are also familial in this breed. Bernese mountain dogs do not appear to have any higher incidence of histiocytoma - a largely benign histiocytic neoplasm of the skin. There are several other breeds that have similar high incidence of histiocytic diseases; these include Rottweilers, Golden Retrievers, and Flat Coated Retrievers. Pedigree analyses have not been exhaustively conducted in these breeds, or if they have, the data is not yet published. Flat Coated Retrievers appear to have a higher incidence of problems with the full spectrum of histiocytic diseases, including histiocytomas which are normally benign in all breeds. We have seen multiple histiocytomas in this breed with metastasis to local lymph nodes and beyond.
A group of related Irish Wolfhounds in the Pacific Northwest has experienced problems with systemic histiocytosis. I am not sure if this is an isolated situation or if this breed is experiencing problems in other areas of the country.
Shar Peis appear to have a higher incidence of problematic histiocytomas with aberrant presentation, especially multiple tumors with delayed regression.
Pembroke Welsh Corgis are over-represented in several case series of primary HS of the central nervous system (CNS) relative to the breed prevalence. This data initially was limited to Japan, but we recently have encountered Corgis with HS of the CNS with high prevalence at UC Davis.