What is Secondary Hypertrophic Osteoarthropathy?
Hypertrophic osteoarthropathy (HOA) is a health condition that involves symptoms like severe joint pain, swollen fingers or toes that look “clubbed” (or rounded), and a thickening of the outer layer of your long bones. Some people may also have extra fluid in their joints.
This condition happens because there’s an unusual increase in the growth of blood vessels and fibrous tissues, which is also known as ‘fibrovascular proliferation’. While it can sometimes run in families due to certain genes (a condition known as pachydermoperiostosis), it’s much more common to develop HOA because of a different ongoing disease. These could be diseases that exist outside of the lungs or chronic diseases and cancer that specifically involve the lungs.
In cases where HOA is tied to lung disorders, it’s also referred to as hypertrophic pulmonary osteoarthropathy (HPOA).
What Causes Secondary Hypertrophic Osteoarthropathy?
In the 1890s, Pierre Marie and Eugen von Bamberger described a condition that is now also known as the Pierre Marie- Bamberger syndrome. They used the term hypertrophic pulmonary osteoarthropathy to describe it because it is commonly associated with lung diseases like lung cancer, cystic fibrosis, or pulmonary tuberculosis. Interestingly, 95 to 97% of cases of this condition actually come from another primary condition, meaning they are secondary.
Hypertrophic osteoarthropathy can cause swelling in multiple bones symmetrically or in one specific area. The majority of this condition, when it affects multiple bones, comes from lung diseases. This is why it is often called hypertrophic pulmonary osteoarthropathy, or HPOA. Yet, there are several non-lung diseases that can also cause this condition.
HPOA can be caused by a variety of lung diseases, like lung cancer, diseases where cancer has spread to another part of the body, mesothelioma and cystic fibrosis. It can also originate from mycobacterium infections like tuberculosis, long-term infections, unordinary connections between arteries and veins in the lungs, and sarcoidosis, an inflammatory disease that affects multiple organs in the body.
Non-lung related causes of HPOA include heart conditions like birth defects, a type of benign heart tumor and infection in the heart’s inner lining; gastrointestinal issues like growths in the colon, cancer, inflammation of digestive tract, difficulty in passing food through the esophagus, and frequent use of laxatives; liver and bile duct related conditions like liver disease, bile duct obstruction in infants, slow long-term liver disease, Wilson disease (an inherited disorder), liver cancer and sclerosis that leads to scars within the bile ducts.
Some other miscellaneous causes include benign tumor in the thymus gland, medical condition known as POEMS syndrome, blood disorder known as myelofibrosis, and blood cancer.
The localized form of HPOA, which affects only a specific part of the body, can be caused by an infected graft to repair blood vessels, inflammation of the walls of arteries, a defect where the blood vessel that allows blood to go around the baby’s lungs before birth doesn’t close and aneurysms which is a bulge in the wall of an artery.
Risk Factors and Frequency for Secondary Hypertrophic Osteoarthropathy
Hypertrophic osteoarthropathy is a condition equally seen in individuals regardless of their race or sex. Usually, it is diagnosed in people aged between 55 and 75 years.
- This condition is commonly linked with cancer, making up 90% of the cases.
- Of these, non-small cell lung cancer, specifically adenocarcinoma, is the usual cause of secondary hypertrophic osteoarthropathy – happening in between 0.7% and 17% of cases.
- Interestingly, while less common overall, hypertrophic osteoarthropathy is more likely to occur in patients with pleural tumors. For example, with 22% of solitary fibrous tumors of the pleura leading to this condition, compared to only 5% in non-small cell lung cancer cases.
Signs and Symptoms of Secondary Hypertrophic Osteoarthropathy
Patients who have periostosis can show a range of symptoms. Some people might not show any symptoms at all, while others might experience a series of recognizable symptoms such as nail clubbing, thickening of bone (periostosis), and fluid-filled swelling around joints (synovial effusions).
If the condition is linked with cancer, patients often report an intense burning sensation in their fingers or toes in the early stages. As the disease progresses, this can turn into severe pain in the long bones of the lower body, and this pain usually gets worse when the body part is hanging down. This kind of pain often leads doctors to mistakenly believe the patient has inflammatory arthritis.
Interestingly, traditional pain killers (opioids) often do very little to alleviate this bone and joint pain, but other types of pain-relieving drugs called NSAIDs can help. When it affects the joints, both sides of the body are typically affected equally and patients can see swelling, but without the tell-tale signs of inflammation like cell infiltration or swelling of the synovial membrane.
Sometimes, other symptoms related to the primary disease can help in diagnosis. For example, if the disease is associated with lung cancer, the patient may also have a new or persistent cough, producing blood when coughing (hemoptysis), or losing weight. If it’s related to Graves disease, a type of thyroid disease, the patient might have prominent eyes (exophthalmos) and skin thickening (myxedema). If it’s related to a liver or gallbladder disease, there could be signs of chronic liver disease or gallbladder disease.
Testing for Secondary Hypertrophic Osteoarthropathy
During a physical exam, your doctor may find some typical signs indicative of certain conditions. An example of this is the “drumstick” appearance of your fingernail beds, which is a sign of clubbing – a condition that causes your nails to thicken and curve around your fingertips. This characteristic look can be seen on both fingers and toes, although it may be less noticeable on the toes due to their normal shape.
In some cases, clubbing could be the only symptom you have. However, it can also lead to a condition known as hypertrophic osteoarthropathy where you may observe a cylinder-like swelling in your legs, often referred to as ‘elephant legs’. You may also notice that the bones in certain non-muscular parts of your body, like your ankles and wrists, have thickened.
Often, you may detect swelling in large joints, particularly in your knees and wrists. When fluid is drained from these swollen joints, it normally has low white blood cell count and may clot spontaneously.
As this combination of symptoms can also be observed in connective tissue diseases, it could be difficult for doctors to diagnose the exact condition. To make things even more complex, this condition could also be associated with a lung cancer that presents with elevated levels of certain antibodies. Currently, there are no specific blood markers for this condition making it problematic to diagnose. Yet, some indirect signs like increased levels of bone formation markers may provide some clues.
Due to these complexities in a clinical diagnosis, medical imaging is largely relied on to identify hypertrophic osteoarthropathy. The key feature to look for in imaging is symmetrical bone thickening in the absence of any bone damage or fracture. This characteristic thickening primarily affects the middle portion of long tubular bones such as the tibia, fibula, radius, and ulna. As the condition progresses, the bone ends also get involved. In advanced stages, multiple layers of the bone get thickened causing an irregular appearance.
MRI imaging can offer more detailed pictures of the bone changes associated with this condition. PET scans can show new bone formation that absorbs a glucose-based solution given before the scan. However, these findings may mislead a doctor to wrongly diagnose a metastatic disease.
Bone scintigraphy, which involves the use of a small amount of a radioactive substance, can provide a clearer picture of this bone condition and is considered the best test. It is very useful as a response marker, highlighting a successful treatment when the radiographic findings disappear. If an X-ray hints towards hypertrophic osteoarthropathy, your doctor may recommend a bone scan in conjunction with a chest imaging to search for the primary cause.
Treatment Options for Secondary Hypertrophic Osteoarthropathy
The management and likelihood of recovery from secondary hypertrophic osteoarthropathy, a disease affecting the bones and joints, primarily depends on the cause of the disease. There are generally two distinct ways of tackling this issue:
1. Addressing the Primary Cause:
The most effective treatment is to cure the root cause of the problem. This could involve various methods such as surgical removal, chemotherapy or radiofrequency ablation if the bone disease is caused by lung cancer. If the patient has conditions like pulmonary tuberculosis or cystic fibrosis, they would be treated with drugs that kill the bacteria causing the tuberculosis or a lung transplantation. Similar, treatments for liver disease involved liver transplants. Some success has also been reported in treating the disease caused by cholestatic cirrhosis, a liver condition, through liver grafts, which is the transplantation of liver cells.
For patients with heart or esophageal diseases, treatments include surgical correction of the heart problem or removal of the esophagus. In situations where the disease is a result of an infection from a vascular graft, a synthetic material used in surgery, the graft is surgically removed and the patient is put on a course of antibiotics. Still, it is important to note that the overall survival rate in such cases is just above half of patients.
2. Managing Symptoms:
In cases where the root cause cannot be cured or treated, managing the patient’s symptoms becomes the primary goal. This can be quite challenging, especially since these patients tend to have severe symptoms due to the advanced stage of their underlying disease. Some techniques used to provide relief include the dissection of the patient’s vagus nerve, which has shown to relieve symptoms. However, this practice has lost favor over time as theories about the cause of the disease have evolved. In recent years, this method was revisited, and was successful in treating a patient with incurable lung cancer.
Another method involves using a regimen of adrenergic antagonists, drugs that block messages to certain receptors in your body, to suppress symptoms. These medications have shown to improve functionality in patients.
Doctors may also prescribe Nonsteroidal anti-inflammatory drugs, commonly known as NSAIDs. Infants with arthritis and periostitis, a condition characterized by inflammation around the bones, have shown a robust response to the NSAIDs, including indomethacin and ketorolac as well as COX-2 inhibitors like celecoxib. They appear to be much more effective than opioid analgesics for managing pain.
Other drugs like Octreotide, used to treat severe diarrhea and flushing caused by cancer, and Bisphosphonates, used to slow down or prevent changes to your bones, have been useful in providing relief to patients. Growing evidence suggests these medications work by reducing levels of a protein called VEGF, which is often high in patients with hypertrophic osteoarthropathy.
There is also ongoing research on using specific inhibitors of this protein, VEGF, combined with traditional chemotherapy drugs for non-small cell lung cancer. These inhibitors offer a promising way to provide symptom relief by blockages in the blood vessels that can cause the disease.
What else can Secondary Hypertrophic Osteoarthropathy be?
When a patient shows signs of multiple bone reactions on an X-ray, doctors need to consider a few possible diagnoses. These might include:
- Thyroid acropathy
- Primary hypertrophic osteoarthropathy
- Blood cell cancers
- Overdosage of vitamin A
- A rare genetic condition known as Camurati Engelmann Disease or progressive diaphyseal dysplasia
It’s also notable that a drug called Voriconazole could cause bone inflammation that appears similar to hypertrophic osteoarthropathy. Frequently, initial diagnoses for these types of symptoms could be inflammatory joint disease, connective tissue diseases, or a related joint disease due to inflamed blood vessels, before the correct diagnosis of hypertrophic osteoarthropathy is confirmed.
What to expect with Secondary Hypertrophic Osteoarthropathy
The results for patients with hypertrophic osteoarthropathy, a condition where bones and joints become thickened and painful, rely heavily on what’s causing it. When it’s linked to a serious condition like cancer, the outcome is usually not favorable despite receiving treatment.
If the root cause of hypertrophic osteoarthropathy is specifically treated, the condition might completely disappear. This usually means that along with curing the underlying issue, the patient is also receiving treatments to relieve the symptoms of the condition.
Moreover, if the symptoms return, it could be an indication that the original medical issue causing the hypertrophic osteoarthropathy has returned or worsened.
Possible Complications When Diagnosed with Secondary Hypertrophic Osteoarthropathy
Secondary hypertrophic osteoarthropathy, a specific type of bone disorder, does not make an existing disease more harmful or deadly. The only risk associated with this condition is the potential development of osteoarthritis if the hypertrophic osteoarthropathy persists for a long time.
Related Risks:
- No increased harm or death risk from the existing disease
- Possible osteoarthritis with prolonged hypertrophic osteoarthropathy
Preventing Secondary Hypertrophic Osteoarthropathy
Most people who have been diagnosed with osteoarthropathy – a condition affecting the joints – often need some sort of comfort in understanding the condition. It’s important for these individuals to know that further tests will be necessary to discover what’s causing the condition. It’s crucial to follow through with these tests so that doctors can identify the correct diagnosis.
Once people understand that this disease is a secondary condition, meaning it is a result of another health issue, it can significantly enhance their willingness to follow the treatment plan. Following the recommended treatments can eventually lead to better health outcomes and improve the overall quality of life.
