The International Association for the Study of Pain (IASP) has drawn up an outline of the sensitive and specific clinical criteria necessary for the diagnosis of CRPS. According to the research institute, the common criteria for the recognition of this disease are: pain, constant, not exclusively due to initial trauma and a list of symptoms that patients diagnosed with CRPS should show such as hyperalgesia (hypersensitivity to pain stimuli); hyperextension (hypersensitivity to touch, allodynia), asymmetry of skin temperature, skin color change, asymmetry of local sweating, edema, reduced mobility, dystonia, tremor, tremor, paresis (in the sense of weakness), changes in hair or nail growth.
To be included in the CRPS category, the patient must have at least one of the symptoms mentioned above. In addition, although not necessary for diagnosis, another factor in the recognition of this disorder for doctors is the measurement of skin temperature with appropriate tools.
To ensure that there is no doubt about the diagnosis of CRPS, the following diseases with similar characteristics to CRPS in particular must be excluded from a differential diagnostic point of view: rheumatic diseases, inflammation (e.g. pathogenic arthritis, postoperative infections, polyneuritis, polyradiculitis, plexus damage), thromboembolic diseases, compartmental and nervous compression syndromes. Laboratory chemical analyses are also used for this purpose. The CRPS symptom itself is not characterized by abnormalities in routine laboratory parameters such as CRP elevation or BSG acceleration. It is often necessary to document the course of the disease through the use of methods used in the case of pain therapy, including pain quantification, functional parameters (strength, range of motion, circumference measurement) and vegetative functional disturbances. The CRPS CSS gravity scale screening allows to document the course of the disease.
Clinical and instrumental confirmation diagnostics
It is quite common during the course of CRPS to find changes in the patient due to other factors. Therefore, it is always useful to document the CRPS affected limb with images that follow the different stages of the disease.
There are some cases, for example, in which results confirming or excluding CRPS diagnosis have been found. If the diagnosis is confirmed, the common factors in patients are an intensification of pressure pain in periarticular structures (pressure hyperalgesia). It is not by chance that in a study carried out on CRPS, it was found that the pressure pain thresholds are calculated on all the interphalangeal joints of the affected hand. According to this study, the metacarpophalangeal joints and the proximal and distal interphalangeal joints were 69% more sensitive than normal in the first year of CRPS. Also according to this study, the measurement of osteo protein in serum could replace or add value to triphase bone scintigraphy. In addition, another method of patient analysis useful for the diagnosis of CRPS is the repeated measurement or long-term measurement of skin temperature in lateral comparison of more than 7 hours, as temperature differences greater than 1° or 2° degrees support the thesis that it is CRPS.
Another useful tool for the diagnosis of CRPS is conventional radiographs, which help to monitor osteoporotic changes in patients, as 50% usually have changes over 4-8 weeks in the form of small spots in the bones near the joints. When considering X-rays, care should be taken because there may be cases where these factors are confused with the symptoms of osteoporosis, which is why it is advisable to prefer bone scintigraphy at an early stage in support of the diagnosis, which should also follow other factors.
CRPS therapy: general recommendations
According to recent studies, it is a common problem to fail to make any distinction between pain efficacy, function or clinical symptoms. There is no doubt that pain reduction in patients with CRPS is the primary goal, while function improvement plays a secondary role.
There are also other modalities of intervention for the treatment of CRPS. There are facilities in which, in addition to pharmacological treatment, psychological support is also provided in cases of patients who also experience mental disorders as a result of the pathology, and others who offer physiotherapy sessions.
The latter are developed in different ways that can be divided into the following phases:
- An initial phase that sees the stimulation of movements in the patient with attention and with the active collaboration of these. Passive measures, taken against the patient’s will and without control, result in an increase in pain, and are therefore contraindicated, as they prevent further patient cooperation, affect CRPS and therefore may make it impossible to return functional through the formation of contractures avoiding movement. Often analgesics are at least partially effective and should be tested to achieve these therapeutic goals.
- In the next phase, greater importance is given to neurological and joint rehabilitation procedures. This gives greater importance to the activation of movement and less importance to pain therapy.
- The third phase focuses on the treatment of functional disorders (movement, sensor technology). In this case, functional-orthopaedic-psychological rehabilitation and psychosocial reintegration play a primary role in treatment. Pharmacological pain therapy is often only necessary to a limited extent.
Emerging treatments for CRPS include:
Neridronate infusions, treatment of choice against CRPS in Italy. Intravenous immunoglobulin (IVIG). Researchers in the UK report that low-dose IVIG reduced pain intensity in a small study of 13 patients with CRPS for 6-30 months who did not respond well to other treatments. Those who received the IVIG had a greater decrease in pain scores than those who received the saline solution in the 14 days following the infusion.
Ketamine. Researchers are using low doses of ketamine, a strong anaesthetic administered intravenously for several days to substantially reduce or eliminate chronic CRPS pain. In some clinical settings, ketamine has been shown to be useful in treating pain that does not respond well to other treatments.
Several studies have demonstrated the benefits of graduated motor imaging for CRPS pain. Individuals do mental exercises that include identifying painful left and right body parts while looking in a mirror and viewing the movement of those painful body parts without actually moving them.
Several alternative therapies have been used to treat other painful conditions. Options include behavior modification, acupuncture, relaxation techniques (such as biofeedback, progressive muscle relaxation and guided movement therapy), and chiropractic treatment.
Paraclinical tests are important to provide information on autonomous, sensory and motor changes. Bone scintigraphy is useful for providing information on vascular bone changes, especially in subsequent stages of the disease. Simple x-rays should only be taken in the chronic phase, when the state of bone mineralization can be assessed. The Quantitative Sensory Test (QST) and the Autonomous Functional Test for these patients has been reviewed in the literature, although it does not fall within the scope of this article to discuss the details of the test.
More recently, there has been a shift towards restoring functional capacity instead of controlling pain as the primary goal of treatment. Physiotherapy is considered one of the key elements of this process. Physiotherapy is an important component of treatment, although aggressive therapy can be harmful in the early stages, when pain levels are high. Although a functional goal is to improve movement and joint strength, passive movements are often too painful and should be avoided in acute patients. passive therapy, followed by active isometric and then active isotonic training, can be pursued when pain levels decrease.
What research is currently underway on CRPS?
Research has shown that CRPS-related inflammation is caused by the body’s own immune response. Researchers hope to better understand how CRPS develops by studying immune system activation and peripheral nerve signalling using an animal model of the disorder. The animal model has been developed to imitate some characteristics similar to CRPS as follows characteristics similar to CRPS following fractures or limb surgery, activating some molecules involved in the process of the immune system.
Limb trauma, such as a fracture, followed by immobilization in a cast, is the most common cause of CRPS. By studying an animal model, researchers hope to better understand the neuroinflammatory basis of CRPS in order to identify the relevant inflammatory signalling pathways leading to the development of post-traumatic CRPS. They will also examine the inflammatory effects of cast immobilization and exercise on the development of painful behaviours and symptoms of CRPS.
Peripheral nerve injury and subsequent regeneration often lead to a variety of sensory changes. Researchers hope to identify specific cellular and molecular changes in sensory neurons following peripheral nerve lesions to better understand the processes underlying neuroplasticity (the ability of the brain to reorganize or form new nerve connections and pathways following nerve cell injury or death). The identification of these mechanisms could provide targets for new drug therapies that could improve recovery after regeneration.
Children and adolescents with CRPS generally have a better prognosis than adults, which can provide guidance on mechanisms that can prevent chronic pain. Scientists are studying children with CRPS, since their brains are more adaptable through a mechanism known as neuroplasticity. Scientists hope to use these findings to develop more effective therapies for CRPS.
Funded scientists continue to study how inflammation and release of adenosine triphosphate (ATP) can induce abnormal connections and signals between sympathetic and sensory nerve cells in chronic pain conditions such as CRPS. (ATP is a molecule involved in the production of energy within cells that can also act as a neurotransmitter. Neurotransmitters are chemicals used by cells in the nervous system to communicate with each other.) A better understanding of changes in nerve connections as a result of peripheral nerve injuries can provide a greater understanding of pain and lead to new treatments.
CRPS Systemic Drug Therapy
In treating the curative treatment for CRPS, we cannot fail to mention the successful pain-relieving drugs used. These include the use of bisphosphonate (in particular, Neridronate) for the treatment of upper and lower limbs in CRPS in terms of pain, function and self-assessment of patients. The way bisphosphonates act sees an inhibitory effect on osteoclast activity, and a long-term anti-inflammatory effect.
Side effects of using bisphosphonates include irritation of mucous membranes resulting in side effects such as nausea, eruption, heartburn, stomach pain or cramps. Oral bisphosphonates should therefore be taken in the morning with a large glass of water. Patients should not lie down for at least half an hour after intake. The most serious side effect is osteonecrosis of the mandible. It is strongly recommended to make a dental appointment at the beginning of therapy.
The only side effects reported from the Neridronate infusions however, were slight fever and flu-like symptoms, excluding all of the syndromes quotes above, that might be found with other bisphosphonates.
According to some studies, other drugs that can bring benefits to patients with CRPS are steroids. In particular, steroids have positive effects in early inflammatory cases, such as redness, overheating, edema. Steroid use has shown good results in the first days of the disease, up to a maximum of three weeks, while in chronic CRPS that last longer than six months, steroids are effective in some cases, but not in all. Therefore, it is not possible to offer a safe recommendation for the dose or duration of therapy and there are no indications for long-term therapy. With reference to the undesirable effects of steroid use, it can be stated that their severity is related to their dosage and prolonged use that exceeds the date suggested by the reference doctor.
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