CRPS in children. Complex regional pain syndrome in children. Is it different from adults?

CRPS in children, is it different from adults ??

Introduction

Complex regional pain syndrome (CRPS) is a clinical disorder characterized by chronic pain, sometimes spontaneous, sometimes provoked by (minor) trauma or operation. The pain is disproportionate to the triggering event. It can be accompanied by sensory, vasomotor, sudomotor and trophic changes.

The diagnosis CRPS is a clinical diagnosis based on the new IASP-criteria, also known as the Budapest Criteria. Generally two different types are distinguished CRPS type I where there is no demonstrable nerve lesion and CRPS type II which results of a nerve lesion. Distinction between type I and II is unclear since nerve deficits are not well described. Additionally CRPS I and II do not differ in clinical presentation and choice of treatment. In literature other subtypes are mentioned, as an adaptation of the Budapest criteria: CRPS “with remission of some features” and CRPS NOS i.e. “not otherwise specified and no other diagnosis better explains clinical features”, meaning that the patient has never been documented to fulfill the new IASP-criteria (Goebel et al., 2021). Important is that none of these criteria have ever been validated for diagnosing CRPS in children. Also other cut off points for children are suggested (Friedrich Y 2019). So overlooking these adjustments, one may wonder if CRPS in children should always be labelled as CRPS NOS.

Figure 1

Now, is CRPS in children different from CRPS in adults ?

Epidemiology studies show that the incidence in children is more rare, around 1.14-1.2/100.000/year whereas in adults there is a range from 5.5 to 26.2/100.000/year (Abu-Arafeh and Abu-Arafeh 2016; Baerg et al., 2022; de Mos et al., 2007). Just like in adults the incidence is three-to eightfold higher in women. In contrary to adults lower extremities are more involved than upper extremities.

Children may present more often with “cold” CRPS, although swelling and sweating may be present. Skin discoloration and change in temperature are often present, but trophic changes to hair and nails are less often present than in adults. What is seen in almost every patient is severe pain (not dermatome determined, but more shaped like a sock or glove) with hyperalgesia and allodynia in such a way that gentle touch as from clothing or blankets cannot be tolerated. In more advanced cases decreased range of motion, muscular atrophy and dystonia can be seen. Prognostic, the syndrome may develop better than in adults but recurrence rates of 25-50% have been described.

Pathophysiology

In the past it has been discussed by pediatric pain specialists if the pathophysiology in children is different from adults but nowadays, although still not completely elucidated, the general consensus now that it is the same. The basis is probably a genetic determined susceptibility followed by an exaggerated inflammatory response after (sometimes minor) trauma or surgery. Peripheral and central sensitization, immune related factors and altered sympathetic nervous system functioning play a role next to psychologic factors. The incidence of psychologic factors is generally not higher than in other chronic pediatric chronic pain states (Lascombes and Mamie 2017; Logan et al., 2013; Stanton-Hicks 2010; Williams and Howard 2016). Furthermore the representation of the limbs on the somatosensory cortex changes which may reverse when the syndrome is cured.

Diagnosis

The diagnosis CRPS in children is, just as in adults, a clinical diagnosis based on the IASP “Budapest” diagnostic criteria although the criteria are not validated for children. Due to heterogeneity of the syndrome also experience of the clinician may be important in recognizing the symptoms.

Until now, no screening tools, laboratory tests or imaging diagnostics are specific to come to the diagnosis (Greenough et al., 2022). Probably due to unfamiliarity with CRPS in children and a lower prevalence there is still a delay before the patient is referred to a pediatric pain center (Kachko et al., 2008; Lascombes and Mamie 2017; Williams and Howard 2016).

Treatment

Due to the lack of evidence-based data there is no standardized treatment for CRPS in children.

Like most chronic pain conditions in children it needs an interdisciplinary approach according a biopsychosocial model. Physiotherapy by means of a graded exposure or graded activity plan next to desensitization is essential although there are no standard protocols on intensity or duration. Also transcutaneous nerve stimulation (TENS) can be used as supportive treatment. Furthermore psychologic interventions through cognitive behavioral therapy to improve pain coping are important to enhance the physiotherapy program and to avoid refusal of the patient to move, because hand or foot is too painful.

Evidence for effective pharmacotherapeutic treatment options are limited. In literature concerning CRPS in adults a plea was made for a more mechanism based treatment where pharmacotherapy for CRPS in children is generally aiming on symptomatic relief (Mangnus et al., 2022; Williams and Howard 2016). In the Netherlands, free radical scavengers (dimethyl sulphoxide, vitamin C and acetylcysteine) are advised, but internationally they generally are not used. More commonly used drugs are paracetamol or non-steroid anti-inflammatory drugs (NSAID’s) but their efficacy is low. In case of neuropathic/nociplastic pain gabapentinoids or tricyclic antidepressants (TCA’s) can be used, the latter specially if there are also sleeping problems. Further agents that are used are lidocaine patch, in case the painful area is limited, or capsaicin crème, used for desensitization and baclofen for dystonia. There is limited evidence for the use of corticosteroids in the acute phase of CRPS. In refractory cases esketamine i.v. can be considered as well as bisphosphonates in case of bone demineralization (Sheehy et al., 2015). In the past different interventional techniques have been used but evidence is weak and therefore interventional techniques are generally discouraged (Zernikow et al., 2012) (Zernikow et al., 2015). Also the use of neuromodulation remains controversial although one review described good results in a limited amount of patients (Karri et al., 2021). On the contrary good results are achieved with intensive interdisciplinary rehabilitation thereapy (Simons et al., 2013).

Conclusion

Complex regional pain syndrome in children requires experienced assessment in a Pediatric Pain Center with an interdisciplinary approach. Education of patients, parents but also professionals about this rare condition is important. The outcome might be better if treatment is started without delay, although evidence for the different treatment modalities is limited and prognosis might be poorer than previously assumed (Tan et al., 2009; Wong et al., 2020).

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