Painful Genetic Diseases
Patients who have painful genetic diseases make up 20% to 30% of my practice. These patients often report to me that they are misunderstood, that they receive poor pain care, that doctors are afraid of them, and that they have not been able to obtain ongoing chronic pain care. Part of the problem is that some medical practitioners, including those in emergency rooms and pain clinics, don’t believe that these genetic diseases cause pain.
Pain practices throughout the United States are now seeing adults with painful genetic diseases (Table 1). Unfortunately, once pain begins, it may be progressive, produce a debilitative clinical state, and be associated with a shortened lifespan. In some disorders, pain may not begin until the patients have grown into adulthood.
I know of no institution or pain practitioner who has made care of painful genetic diseases a cause or an avocation. This is particularly unfortunate because it is my opinion that pain practices everywhere are now encountering patients with painful genetic diseases, but we really don’t know much about them. One thing, however, is clear: these unfortunate individuals need pain care. What’s more, an aggressive, palliative form of care may be required, since genetic diseases are not curable and are usually progressive as patients age.
Here are a few things we do and don’t know. First, the incidence and the percentage of patients who develop chronic pain with these conditions are largely unknown or are rough estimates, at best. Painful genetic disease may be unappreciated as a cause of pain when an afflicted patient presents for pain treatment. The patient’s initial complaints may be similar to those of a chronic widespread pain, headache, arthritis, or neuropathic patient.1
The most common painful genetic disease is probably kyphoscoliosis. The medical definition of kyphoscoliosis is a combination of outward curvature (kyphosis) and lateral curvature (scoliosis) of the spine. Kyphosis can cause back pain, muscle fatigue, and stiffness on the mild side of the spectrum. In severe cases, it can cause chest pain and make breathing difficult.
Other well-known painful genetic diseases include sickle cell disease and Ehlers-Danlos, or the “hypermobility syndrome.” While many painful genetic diseases, such as Marfan syndrome, dwarfism, or elephantiasis, are obvious on physical exam, sickle cell and Ehlers-Danlos patients may, on general inspection, appear normal.1
Categories of Genetic Diseases
I recommend that painful genetic diseases be placed in 1 of 3 categories:
- Connective tissue
Just how do genetic diseases cause pain? The mechanisms by which pain develops are somewhat unclear. For example, connective tissue diseases usually cause an erosion of soft tissues at some point in the patient’s life. This includes nerves, ligaments, tendons, cartilage, and fascia. Ankylosing spondylitis affects the spinal column, sacroiliac joints in the pelvis, hips, shoulders, and other joints. Early diagnosis and treatment is important to help slow disease progression, which may lead to irreversible autofusing of the spine’s vertebral bodies and joints. April is Ankylosing Spondylitis Awareness Month, so Practical Pain Management is featuring an article about Grammy award–winning musician Dan Reynolds of Imagine Dragons, who is using his voice to bring attention to the disease, which affects him and 2 of his brothers
Metabolic genetic diseases, with the possible exception of sickle cell disease, cause pain by mechanisms that are unclear. Sickle cell disease is known to produce thrombohemorrhagic events that may destroy nerves and other soft tissue. By contrast, the mechanism by which porphyria may permanently destroy membranes and nerves is uncertain. Acute intermittent porphyria (AIP), for example, is the most common porphyria. The presenting symptom is abdominal pain, but pain in the chest, back, or lower extremities may also occur. According to a recent study, “once suspected, the diagnosis of porphyria can be rapidly established by checking random urinary porphobilinogen. Initial management of acute porphyria includes discontinuation of all potentially harmful drugs and management of symptoms. Acute attacks should be treated emergently with intravenous heme and glucose to avoid considerable morbidity and mortality.”2
Some painful neurologic diseases cause degeneration and dysfunction of neural pathways, which results in abnormal or absent nerve conduction. In the case of familial amyloid neuropathy, treatment is directed at both preventing further deposition of amyloid in peripheral nerves and treating painful symptoms. “Depending on the type of amyloid protein, patients may benefit from liver or bone marrow transplant. Neuropathic pain due to amyloid neuropathy can be treated with antiseizure medications, antidepressants, or analgesics, including opioid medications.”3
A major point to be made about painful genetic diseases is that pain will almost always worsen as the patient ages. Dosages and potency of medications may have to be increased. The natural inclination of pain practitioners to taper or reduce opioids and other analgesics may be very inappropriate as the underlying genetic disease may progress over time, increasing tissue destruction and pain. Although painful genetic diseases are not curable, pain practitioners should attempt to develop some innovative dietary, hormonal, or exercise measures that assist symptomatic analgesia and perhaps retard deterioration.