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,
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 histiocytic sarcoma
(better prognosis if treated early), and disseminated histiocytic sarcoma (HS)- this is also
commonly referred to as malignant histiocytosis (MH). Disseminated HS and MH are invariably
fatal regardless of therapy, 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 and MH 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. In systemic histiocytosis, 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 cutaneous histiocytosis are often bright, alert and outwardly
unaffected by their disease. In contrast, dogs with systemic histiocytosis, are often anorexic and lose weight; they may be clinically
depressed as well. This reflects the more aggressive and widespread tissue involvement in systemic histiocytosis.
Neoplastic histiocytic disease (the histiocytic sarcoma complex) 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 HS, the masses can encircle
joints and cause lameness. In other instances, histiocytic sarcoma and malignant histiocytosis affect internal organs and spare 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 constant finding unless the histiocytes manifest
aggression toward red blood cells - this is seen in the hemophagocytic histiocytosis - 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 histiocytic sarcoma 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 cause further respiratory distress. Primary histiocytic sarcomas in bone marrow are usually silent unless the histiocytes are hemophagocytic, or if the site strategically located - eg a vertebral body lesion can destroy the bone and put pressure on the spinal cord. Primary histiocytic sarcomas in brain do occur and can result in paresis, paralysis and seizure activity depending on location.
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% in our series). More potent systemic immunosuppression is then
required. We have used Cyclosporin A (Sandimmune or Neoral) or Leflunomide (Arava) by oral administration. These drugs are well tolerated,
but they are expensive - especially Leflunomide, which is the drug of choice ($1000 to $3000 per month depending on the dog's weight and
drug metabolism). 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 XIII, WB Saunders, 2000.
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 (malignant histiocytosis) 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. Reports of successful treatment of malignant histiocytosis have appeared - without fueling a
controversy, let me simply say that a careful reading of one prominent report left me doubting the validity of the initial diagnoses. You must
keep in mind that there is much confusion out there and many pathologists are not comfortable in distinguishing reactive histiocytic disease from
histiocytic sarcoma complex. Hence, at the moment there is no VALIDATED, efficacious chemotherapy protocol.
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 can 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 malignant 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 organ
failure and death which is commonly seen in malignant histiocytic diseases.
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.
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. OK - So what are histiocytes anyway?
Histiocytes are leukocytes ("white cells") that occur in tissues. Histiocytes include 2 major lineages of cells - macrophages
and dendritic cells - they are very important in the immune system. Macrophages remove cell debris,
foreign material and clear intracellular pathogens. Dendritic cells ensure that T lymphocytes respond
correctly to molecules recognized as foreign (eg peptides derived from pathogens), or altered self
(eg mutated peptides derived from cancer cells). So, histiocytes are integrally involved in the function of the immune system. In fact,
one form of histiocytosis - the reactive form ( or cutaneous and systemic histiocytosis) - occurs as a result of a defect in the interaction
of dendritic cells and T lymphocytes - an immuno-regulatory disorder which is amenable to treatment with immuno suppressive drugs.
Q10. Are Bernese Mountain Dogs the only breed affected by histiocytic diseases?
Bernese Mountain Dogs have a staggering incidence of histiocytic diseases, especially the reactive histiocytic diseases - cutaneous
and systemic histiocytosis, and the neoplastic histiocytic diseases - the histiocytic sarcoma complex. These diseases are also
familial in this breed. Bernese Mountaind 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
Q11. My Bernese Mountain Dog has a malignant form of histiocytic disease - I am devastated by the thought of losing a family member - how can I make difference for other afflicted dogs in the future?
When it is time to euthanize your Bernese Mountain Dog you could contact Dr. Verena Affolter (email@example.com) or Dr. Peter Moore (firstname.lastname@example.org)
to check if we have a current need for diseased tissue. If so, your veterinarian could contact us to arrange for tissues to be sent for future
research into underlying causes of histiocytic sarcoma complex. The laboratory telephone number is 530 752 6611. If you would like to
accelerate this research, and are willing and able to financially support the ongoing work you should contact The Center for Companion
Animal Health, School of Veterinary Medicine. We have developed a list of projects with descriptions that are planned or in progress so
that you can choose to support a project that most interests you. Your support will make a difference - for instance, it can be used as matching
funds to enhance the chances of getting an extramural grant funded!