Modern Principles of Diagnosis and Treatment in Complex Regional Pain Syndrome

Background: Complex regional pain syndrome (CRPS) is a relatively common complication, occurring in 5% of cases after injury or surgery, particularly in the limbs. The incidence of CPRS is around 5–26/100 000. The latest revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) now categorizes CRPS as a primary pain condition of multifactorial origin, rather than a disease of the skeletal system or the autonomic nervous system.

Method: Based on a selective search of the literature, we summarize current principles for the diagnosis and treatment of CRPS.

Results: Regional findings in CRPS are accompanied by systemic symptoms, especially by neurocognitive disorders of body perception and of symptom processing. The therapeutic focus is shifting from predominantly passive peripheral measures to early active treatments acting both centrally and peripherally. The treatment is centered on physiotherapy and occupational therapy to improve sensory perception, strength, (fine) motor skills, and sensorimotor integration/ body perception. This is supported by stepped psychological interventions to reduce anxiety and avoidance behavior, medication to decrease inflammation and pain, passive physical measures for reduction of edema and of pain, and medical aids to improve functioning in daily life. Interventional procedures should be limited to exceptional cases and only be performed in specialized centers. Spinal cord and dorsal root ganglion stimulation, respectively, are the interventions with the best evidence.

Conclusion: The modern principles for the diagnosis and treatment of CRPS consider both, physiological and psychological mechanisms, with the primary goal of restoring function and participation. More research is needed to strengthen the evidence base in this field.

In 1994, after a number of previous different historical terms (e1, e2, e3, e4, e5, e6, e7, e8, e9, e10), complex regional pain syndrome (CRPS) was conceptualized for the first time by the “International Association for the Study of Pain” (IASP) (e10). Consensus criteria were established ten years later. They were revised in 2010 and slightly adapted in 2021 (Box 1) (1, 2).

Box 1

Budapest criteria

The penultimate revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-9) had still classified essentially identical clinical conditions as “sympathetic reflex dystrophy” or “algoneurodystrophy”. On the one hand, ICD-10 mentions “neurodystrophy/algodystrophy” (which included sympathetic reflex dystrophy, Sudeck’s bone atrophy, shoulder-hand syndrome), while using the term “causalgia” if it developed after a nerve injury. In 2019, the term CRPS was included in the ICD-10. A distinction was made between Type 1 without nerve injury and Type 2 with nerve injury. Only shoulder-hand syndrome remained as “neurodystrophy/algodystrophy”.

On 1 December 2022, ICD-11 came into effect and is meanwhile also available as a German draft version (3, 4). It assigns both CRPS types and, for the first time, shoulder-hand syndrome together to a new symptom category—with a cross reference to chronic postoperative/post-traumatic pain (3, 4). “Chronic primary pain” now comprises, in addition to CRPS, other regional and widespread pain syndromes, such as chronic widespread pain/fibromyalgia syndrome, chronic primary low back pain, chronic primary visceral pain, and chronic primary headache. Common features, such as persistency, high emotional burden, and significant functional limitations are highlighted (2, 3, 4, e11). Chronic primary pain is referred to as “multifactorial” and sometimes as “nociplastic”, as opposed to nociceptive (thermic, mechanical) pain and neuropathic (nerve injury) pain (3, 4, e11, e12, e13, e14). “Nociplastic” is understood as a potentially reversible central hypersensitivity to stimuli without tissue or nerve damage (e12, e13, e14, e15, e16, e17, e18, e19, e20). Indeed, the mechanisms of developing CRPS are nowadays assumed primarily to be peripheral, spinal, and cerebral sensitization processes due to neurogenic inflammatory (auto-)immune response, autonomic dysregulation, and maladaptive protective behavior (learned disuse) (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, e15, e21, e22, e23, e24, e25).

What are the implications of the new ICD-11 conceptual framework for clinical practical diagnostic and therapeutic strategies for CRPS?

Methods

The present review article takes a clinical interdisciplinary view of new diagnostic aspects and function-focuseded forms of treatment of CRPS. It follows the current German (15) and international CRPS guidelines and expert recommendations (16, 17, 18). A selective literature search was also conducted in PubMed for original articles and reviews published in English or German relating to the clinical presentation, course, (differential) diagnostics, and treatment of CRPS in adults. The search terms were “CPRS”, “complex regional pain syndrome”, “diagnosis”, “treatment”, “guideline”, “consensus”, and “recommendation”. The clinically most useful articles are cited directly, and a list of further reading is provided as e-references.

Diagnosis

Incidence, inciting causes, risk factors

The incidence of CRPS is between 5 and 26 per 100 000 per year, its prevalence is about 20/100 000 (19, 20); numbers fluctuate strongly, depending on diagnostic criteria (8, 19, 20). Women are more commonly affected than men, with a ratio of 2–4 : 1 (19, 20, 21, e26, e27, e28). The age peak is around the 40th to 70^th year of life (19, 20, 21, e26, e27, e28). However, CRPS occurs at any age, also affecting children and adolescents at a rate of about 1 to 5 per 100 000 (19, 20, 21, e26, e27, e29, e30).

In 0.2 to 9% of cases, CRPS develops after peripheral fractures or ligament injuries, in 2 to 5% after nerve injury, and in 1 to 13% after surgery of the extremities (8, e22, e23, e24, e25, e28, e31, e32, e33, e34, e35, e36, e37, e38, e39). On the other hand, 40 to 50% of all CRPS cases are preceded by fractures, and 30 to 40% are the result of other injuries or surgical procedures (1, 8, 19, 20, 21, e26, e27). Type and degree of tissue or nerve damage, immobilization, and high initial pain intensity increase the risk of developing CRPS (Box 2) (e28, e34, e35, e36, e37, e38, e39, e40, e41, e42). Yet even mild tissue injury can result in CRPS, for example, following arthroscopy, tourniquet application, snowball injury, injection, vaccination, or local infection (19, 20, e26, e27, e43, e44, e45). CRPS of the limbs (e.g., shoulder-hand syndrome) can also follow cerebral, spinal, and cardiac ischemia, degeneration, injuries, surgical procedures and, in isolated cases, malignant neoplasm, even though the tissue injury may lie far proximal to the site of manifestation (20, e27, e41, e46, e47, e48, e49, e50, e51, e52, e45, e46, e47, e48, e49, e50, e51). No initial event is clearly defined in about three to ten percent of cases (19, 20, 21, e27, e53). Painful pre-existing conditions (e54, e55, e56, e57) and stressful life events (6, 22, e58, e59), even without tissue injury (6), can precede CRPS (Box 2).

Box 2

Potential risk factors for developing CRPS

There is conflicting data on psychological risk factors for developing CRPS. Overall, the rate of premorbid and comorbid post-traumatic stress disorders (PTSD) appears to be increased: 27 to 38% fulfill all, 56% most criteria (22, e59). Anxiousness and pain catastrophizing appear to both increase the risk of disease (e60) and worsen its prognosis (e61, e62, e63). Most studies, however, do not show an increased rate of depression, anxiety disorders, or personality disorders as compared with other diseases (22, e33, e37, e42, e57, e58, e59, e60, e61, e62, e63, e64, e65, e66) (Box 2).

Clinical presentations and diagnostic criteria

The cardinal symptoms of CRPS are regional pain and other sensory, motor, autonomic, and trophic disturbances (Box 1). Distal extremities are by far the most common sites of manifestation of CRPS, with the hands being affected more often than the feet. The symptoms have a “glove-” or “sock-like” distribution and do not correspond to a dermatome or area of innervation. There have been isolated reports of CRPS affecting, amongst other sites, the face and trunk (e45, e67, e68, e69).

To establish a CRPS diagnosis, the Budapest criteria must be met—as per the current guidelines, too (Box 1) (1, 2, 3, 4, 15, 16, 17, 18). Their sensitivity is around 98 to 99%, their specificity about 36 to 68% (1, 8, e46, e57). The entry criterion is continuing pain disproportionate to any inciting event (in 1994 it was still “harmful event or immobilization” [e10]). Neither the disproportionality nor the potential inciting cause is defined more precisely. No other disorder, including the primary injury, better explains the signs and symptoms (1, 15, 16, 17, 18). There is no time criteria; the CRPS guideline of the German Neurological Society (DGN) specifies two to three months as a reasonable time point (15) by which all criteria must be fulfilled, bearing in mind that the healing process of the primary injury still needs to be awaited.

The majority of patients present other symptoms, in particular top-down disturbances of body perception and symptom processing (7, 8, 9, 10, 11, 12, 15, 16, 17, 22, 23, e70, e71, e72, e73, e74, e75, e76, e77, e78, e79, e80, e81, e82, e83, e84, e85, e86, e87, e88, e89, e90, e91, e92, e93, e94, e95, e96, e97, e98, e99, e100, e101, e102, e103, e104, e105, e106, e107, e108) (Box 3). For example, between 32 and 84% have neuropsychological symptoms relating to the affected limb, i.e., disturbances of alertness/attentiveness, sense of body ownership/sense of position, experience of authorship/control of actions, and attribution of meaning/emotions (7, 23, e69, e70, e71, e72, e73, e74, e75, e76, e77, e78, e79, e80, e81), even in the form of depersonalization (e82) or alexithymia, i.e., a reduced ability to identify emotions experienced by themselves and others (e83). A combination of finger misperception and body image disturbance differentiated between patients with CRPS and those with fractures with a specificity of 85% and a positive predictive value of 84% (e84).

Box 3

Additional clinical findings in CRPS

There appear to be clinical, possibly pathophysiological, overlaps with neuropathic pain syndromes (15, 16, 17, 18, e101, e102, e103), as well as with other chronic primary pain syndromes (3, 4, 18, e11, e12, e13, e14, e104, e105, e106, e107, e108) and functional (e18), (especially functional neurological) disorders, defined as involuntary discontinuity of the normal integration of motor, sensory, cognitive functions (7, 9, 11, 12, e109, e110, e111, e112, e113, e114), and PTSD (6, 22, e59, e80). Modern guidelines recommend assessing affective disturbances and body perception disturbances, especially post-traumatic stress symptoms, attentional disturbances, fear of touch or of movement (15, 16, 17, 18). So far, however, such features have not been included in any diagnostic criteria (1, 2, 3, 4) (Box 3).

Technical and laboratory findings are not included in the diagnostic criteria either (1, 2, 3, 4): CRPS is and remains a clinical diagnosis. If history and clinical examination have established the diagnosis, then no guideline recommends any further diagnostic investigations (15, 16, 17, 18). To help substantiate the diagnosis, the DGN CRPS guideline recommends a three-phase bone scan only during the first year of disease in cases of doubt or if an expert opinion is required in the foreseeable future (15). Additional diagnostic investigations, however, allow sound differential diagnostics in accordance with the 4^th Budapest criterion (eBox) (15, 16, 18, e115, e116, e117, e118, e119, e120, e121, e122, e123, e124, e125, e126).

eBox

Technical investigations, useful for differential diagnostics of CRPS*

Subtypes, clinical course, prognosis

Differentiation between CRPS 1 and 2 is controversial, given that, clinically, there is no difference (2, 8, 15, 16, 17, 18, e28). Modern guidelines do not express any difference in recommendations between the two (15, 16, 17, 18). The distinction between “warm” and “cold” CRPS subtypes or stages, however, is of some clinically relevance with regard to treatment (see below) (8, 15, 17, e127, e128, e129). The “warm” subtype is often described as “red”, “sweaty”, and “early”. The “cold” subtype is characterized as “blue”, “dystrophic/atrophic”, “late” and regarded as having a less favorable prognosis. Depending on the situation, vasomotor and sudomotor symptoms, such as skin color changes and sweating, may fluctuate (2, 3, 4, 10, 13) as an indication of central neurogenic regulation – there is possibly a peripheral inflammatory etiology behind “warm” CRPS signs and symptoms, while “cold” CRPS is of a central nervous nociplastic origin (13, e21). The DGN CRPS guideline refers to acute (less than 6 months) as opposed to chronic CRPS (15), while current US-American and British recommendations distinguish between early (less than 18 months) and persistent CRPS (18). New CRPS subtypes (“CRPS with remission of some features” and “not otherwise specified”) were proposed for subsyndromal courses which no longer fully meet the diagnostic criteria or never have (2).

CRPS usually settles within three to 13 months, sometimes even without treatment (20, 21, 24, e28, e74, e130, e131). Complete remissions are rare, though, and difficult to define (21, 24, e132). In more than one half of adult patients at least some of the signs and symptoms persist, especially pain and motor symptoms (20, 24, e28, e74, e130). Although most patients return to work, one third require workplace adaptations, and one third remain permanently unfit for work (20, 24, e74, e130). In about 7%, the CRPS spreads to involve other limbs without any further traumatic event (2, 16, 17, e74, e133, e134).

Differential diagnostic challenges

The differential diagnosis of CRPS is wide-ranging, which inevitably carries with it the risk of being missed or even becoming subject to diagnostic inflation or a diagnosis of convenience (Table 1) (15, 16, 17, 20, 25, e135). Findings are sometimes difficult to objectify, resulting in discrepancies between history and examination as well as between one examination situation to another (2, 15, 16, 17, 18, 25, e136). The fact that the CRPS diagnostic criteria demand that the pain should be disproportionate to the inciting event can lead to it being wrongly attributed to trivial trauma (11). Focus is therefore on a detailed history, clinical examination, and differential diagnostic considerations from an interdisciplinary perspective, together with a careful assessment of the primary injury and repeated (photographic) documentation (2, 15, 16, 17, 18, 25). The Budapest criteria are assessed in comparison with the healthy side, paying due respect to risk factors and additional symptoms (Box 1, Box 3).

Table 1

Subspecialties involved in interdisciplinary clinical diagnostic workup of complex regional pain syndrome (CRPS)

A particular distinction must be made from rheumatic, vascular/vasomotor, infectious, (functional) neurological, psychosomatic/psychiatric disorders, and complications from previous treatment (Table 1) (11, 15, 16, 17, 20, 25, e23, e24, e25, e110, e111, e112, e113, e114, e135, e136, e137, e138, e139, e140, e141, e142). The longer CRPS has been present, the more difficult is the differentiation from chronic non-use/underuse of other origin (15). Referral to an interdisciplinary center should be arranged if there are any doubts, complications (symptom spread, fixed dystonia, skin lesions/infections, malignant edema, severe psychological burden, desire for amputation), or no improvement after about two months (15, 16, 17, 18) (Table 1).

Examinations in the medicolegal setting reveal high rates of simulation, somatoform/functional disorders, opioid dependency (e143, e144, e145), as well as deterioration of signs and symptoms instead of improvement over time (e136). For the purposes of an expert opinion with near complete proof of causality, the diagnosis of CRPS is often insufficient: The German pain assessment guideline refers to CRPS as an “extraordinary chronic pain syndrome” and a “special case”, and rejects trivial trauma as a negligible and interchangeable cause (e135, e146). For confirmation of a comprehensible causal relationship, it demands a (contentiously early) onset of symptoms within a few days to two weeks after the inciting event.

Treatment

Treatment is centered around an inflammatory and particularly sensitive acute phase and an early and late rehabilitation (Table 2) (15, 16, 17, 18, e147). Prior to that, it is worth considering prevention even before CRPS becomes manifest. The key therapeutic principle is functional restoration, guided by graded occupational therapy and physiotherapy—Harden et al. (18) even spoke of “reanimation”. This is facilitated by psychological, physical, pharmacological, and, in individual cases, invasive pain management (15, 16, 17, 18). The primary therapeutic goal is a lasting improvement of function and participation. With this in mind, chances and risks of all therapeutic measures must be weighed up against each other. Possible barriers to recovery, including iatrogenic issues, must be taken into account (15, 16, 17, 18). Throughout every phase of treatment, all passive, fear or pain amplifying, and movement restricting measures against the patient’s will or outside the patient’s control, including unannounced touching and nocebo messages, are contraindicated (15, 16, 17, 18).

Table 2

Principles of staged treatment of complex regional pain syndrome (CRPS) *

Prevention

Of central importance are as little tissue traumatization and immobilization as possible, adequate pain relief, and detailed information for the patient with regard to normal findings and ranges of movement (Table 2) (8, 15, 16, 17, 18, e23, e24, e25, e125, e148, e149, e150, e151, e152, e153, e154). The incidence of CRPS after radius fractures appears to fall if patients are taught light range-of-motion exercises early on (e153); physiotherapy and occupational therapy, together with explicit motor imagery (see below), appear to reduce pain and improve function (e154). There is some controversy concerning any preventive anti-inflammatory effect of ascorbic acid (16, 17, 18, e155, e156); this agent does not find mention in the DGN CRPS guideline (15).

The treatment of manifest CRPS

Treatments are usually delivered within individually tailored, multimodal programs that have been shown to be effective (15, 16, 17, 18, 26, 27, 28, e23, e24, e25, e146, e157, e158, e159, e160, e161, e162). Available data supporting specific individual interventions (see below) are insufficient, comprising only a few randomized controlled trials, mostly involving small or (considering the low specifity of diagnostic criteria) heterogeneous populations (Table 2).

Active forms of treatment

Physiotherapy and occupational therapy

The key recommendation of current guidelines throughout all treatment phases is physiotherapy and occupational therapy, together with neurocognitive elements or components of behavioral therapy aiming at the normalization of sensorimotor integration. This is achieved by graded exposure to strength and movement as well as visuo-tactile stimulation and discrimination (Table 2) (8, 15, 16, 17, 18, 29, 30, 31, e23, e24, e25, e163, e164, e165, e166, e167, e168, e169, e170, e171, e172, e173, e174, e175, e176, e177, e178, e179, e180, e181, e182, e183, e184, e185):

• The Perfetti method and graded motor imagery are directed towards cortical reorganization by means of left-right discrimination training (recognizing photos of limbs in different positions of function), explicit motor imagery, and mirror therapy (projecting the healthy, positively connotated limb onto the affected side) (8, 15, 16, 17, 18, 29, 30, 31, e23, e24, e25, e80, e163, e164, e165, e166, e167, e168, e169, e170, e171, e172). The patient is introduced as early as possible to individual leisure activities/work requirements by self-exercises, also with the help of computer applications (e173, e174, e175, e176, e177, e178, e179, e180, e181). Mirror therapy appears to be particularly effective for post-stroke CRPS (15, 29 e168), but it is not sufficient on its own for the majority of cases. Indeed, mirror therapy can even make individual cases worse, or result in the development of symptoms on the contralateral side, (15, 29, e169). Overall, neurocognitive procedures appear to improve function more than alleviate pain (27, 29, e169).
• There is adequate proof that graded exposure can improve function, pain, and fear (15, 16, 17, 18, 26, e182). Perceptual disturbances, kinesiophobia and dysfunctional protective behavior are adressed and gradually reduced by graded exposure and the violation of dysfunctional expectations. In such an approach, occupational therapy, physiotherapy and psychology work closely together.

Pain exposure without psychological support is a subject of controversy because of frequent discontinuations of treatment; therefore, it is no longer recommended (15, 18, 26, 31). Self-efficacy, fitness and body-mind techniques, integrated into an overall treatment concept which includes playful or meditative methods, often in groups, can additionally improve body perception and control in a cost-effective way with few side effects (Table 2, 16, 17, 26, e24). Studies dealing with this, however, are lacking.

Psychological treatment

Current guidelines recommend stepped psychological interventions (Table 2) (15, 16, 17, 18):

• Teaching a biopsychosocial explanatory model which provides motivation and instructions for the best possible active and fear-free use of the limb (psychoeducation) is conducted immediately by the attending “somatic” healthcare staff (15, 16, 17, 18, e152, e153). For this purpose, patients need information, repeated often and in reassuring, layman’s language, which they can then put into action.
• Within the framework of multimodal treatment, clinical psychologists conduct a more differentiated form of psychological pain therapy, oriented predominantly towards cognitive behavioral therapy and often also in groups to enable exchange with fellow patients (15, 16, 17, 18).
• Guideline-based psychotherapy provided by board-certified medical/psychological psychotherapists may be indicated for intractable cases and patients with considerable biographical or current stresses and strains and/or mental comorbidity (15, 16, 17, 18).

However, the level of evidence covering psychoeducative/psychological and, above all, psychotherapeutic interventions for CRPS is low and for the most part derived from other chronic pain disorders (8, 15, 16, 17, 18, 34, e23, e24, e25, e159, e186, e187, e188, e189, e190, e191, e192).

Passive forms of treatment

Medication

The focus of pharmacotherapy (eTable 1) is also primarily on maintaining function (15, 16, 17, 18): Sedatives, for example, improve tension and sleep disturbances, yet interfere with treatment cooperation and participation (fitness to drive!). It is important to inform patients in detail about risks/side effects, the need to gradually increase the dose until adequate levels are reached, to consider a possible delayed, sometimes absent, effect, and to discontinue or withdraw if necessary (15, 16, 17, 18, 34, e193). Medication needs decrease and self-efficacy improves by incorporating active, non-pharmacological interventions such as relaxation methods.

eTable 1

Pharmacotherapy of complex regional pain syndrome (CRPS)

Pharmacotherapy is based almost without exception on off-label drugs where evidence is limited (eTable 1) (8, 15, 16, 17, 18, 26, 27, 28, 32, e23, e24, e25, e194, e195, e196, e197, e198, e199, e200, e201, e202, e203, e204, e205, e206, e207, e208, e209). Current treatment recommendations vary: The German guideline recommends anti-inflammatory bis-phosphonates and steroids which are of equal value for the acute inflammatory phase (15), the British guideline recommends only bisphosphonates (16), while the position paper of the European Pain Federation recommends neither (17). The DGN CRPS guideline regards oral pain pharmacotherapy as a basic measure (15) and recommends gabapentinoids with some reservations and ketamine with strict indications (15). Other guidelines are more cautious and recommend prescribing analgesics only when stopping rules are established due to their frequent ineffectiveness and side effects (17) or only when functional restoration is not possible without them (18). Beyond that, many guidelines refer to the more established treatment recommendations that exist for neuropathic pain (for example, the use of gabapentinoids, antidepressants, possibly botulinum toxin, 15, 16, 17, 33, e209), although even CRPS 2 only partially meets the definition of neuropathic pain (18, e210).

Current guidelines hardly mention the use of topical agents with their various chemical properties (15, 16, 17, 18). Their advantage lies in their minimal side effects. In addition, the tactile stimulus when applied by the patients themselves provides better somatotopic representation and motor control. The German guideline points out that dimethyl sulfoxide cream is standard therapy in the Netherlands (15, 26). Other substances with an effect on the central nervous system, such as naltrexone and memantine, as well as immunomodulatory drugs are regarded as experimental and thus not yet recommended (15, 16, 17, 18, 26, 27, 28, 32, e24, e160, e211, e212).

Physical therapy and medical aids

Passive physical measures, including transcutaneous electrical nerve stimulation (TENS) and acupuncture, are directed primarily at edema and pain relief, and medical aids towards better functionality (Table 2). According to modern guidelines, manual lymphatic drainage is suitable for edema treatment (15, 17), while other procedures are either not mentioned at all or only briefly touched (16, 17, 18, 26). There are hardly any studies on this, and these are contradictory. (15, 16, 17, 18, 26, 27, 28, e24, e213, e214, e215, e216, e217).

Interventional therapies

Where interventional measures reduce—albeit temporarily—pain and restricted movement, they open a window of opportunity for active rehabilitation. Given that they are associated with higher costs, risks and, possibly, repeated experience of pain and helplessness, however, they require a strict indication, especially when they are demanded by the patients themselves (15, 16, 17, 18). They are reserved for unequivocal, severe CRPS where conservative measures have been exhausted (15, 16, 17, 18).

According to current guidelines, including the DGN CRPS guideline, there is the option of spinal cord stimulation for intractable CRPS of the lower limbs (eTable 2) (15, 16, 17, 18, 26, e218). Recent reviews and a current randomized comparative study suggest that direct dorsal nerve root stimulation has probably fewer side effects and is longer lasting than spinal cord stimulation (15, 18, 34, e219, e220, e221, e222, e223, e224). Intrathecal baclofen may be considered for intractable dystonia (15, 16, 18). So far the evidence is not convincing for any other approaches; for example, with regard to the duration of action of transcranial magnetic stimulation, and the risk-benefit profile of more invasive methods (eTable 2) (15, 16, 17, 18, 26, 27, 28, e23, e24, e25, 34, e225, e226, e227, e228, e229, e230, e231, e232, e233, e234, e235, e236, e237).

eTable 2

Technical or invasive interventions for complex regional pain syndrome (CRPS)

Future prospects

Peripheral and central, physiological and psychological mechanisms appear to work together in CRPS. Diagnosis specificity and treatment effectiveness seem to improve when neuropsychobehavioral findings are taken into consideration. This is reflected in modern guidelines and the IDC-11, but not yet in the CRPS diagnostic criteria. Sensitive early warning signals, specific clinical criteria and biomarkers, as well as properly targeted prevention/treatment strategies should be further developed—while still maintaining a differentiated look at comorbidities und differential diagnosis.

Conflict of interest statement

Dr. Böhringer received fees from Grünenthal for a presentation.

Prof. Hausteiner-Wiehle received lecture fees and reimbursement of travel expenses from Windach Hospital and the Lindau Psychotherapy Weeks.

Alexandra Melf-Marzi and Dr. Wiehle declare that no conflict of interest exists.

Manuscript received on 21 April 2022, revised version accepted on 17 October 2022.

Translated from the original German by Dr. Grahame Larkin MD

Corresponding author
Prof. Dr. med. Constanze Hausteiner-Wiehle
Department for Neurology, Clinical Neurophysiology and Stroke Unit

BG Trauma Center Murnau, Prof.-Küntscher-Strasse 8, 82418 Murnau

Cite this as:
Melf-Marzi A, Böhringer B, Wiehle M, Hausteiner-Wiehle C:

Modern principles of diagnosis and treatment in complex regional pain syndrome.

Dtsch Arztebl Int 2022; 119: 879–86. DOI: 10.3238/arztebl.m2022.0358

►Supplementary material

eReferences, eTables, eBox:
www.aerzteblatt-international.de/m2022.0358

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This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet: cme.aerzteblatt.de. The deadline for submission is 26 December 2023.

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