A Case of Complex Regional Pain Syndrome With Hypermobile Ehlers-Danlos Syndrome and Mast Cell Activation Syndrome: The Role of Unconventional Therapies

Abstract

Complex regional pain syndrome (CRPS) type 2 is a chronic pain condition that develops after a nerve injury and is characterized by severe pain, allodynia, and functional impairments. Ehlers-Danlos syndrome hypermobility type (hEDS) and mast cell activation syndrome (MCAS) are connective tissue and inflammatory disorders that may contribute to the development of CRPS. Despite various treatment approaches, effective pain management remains a challenge, particularly in complex cases involving underlying genetic predispositions. We report the case of a 42-year-old female with a history of CRPS type 2, who was recently diagnosed with hEDS and had a family history of MCAS. Her clinical symptoms of chronic pain and gastrointestinal (GI) disturbances were unresponsive to typical therapeutic interventions. She was being managed with multiple medications. With this thought in mind, montelukast, a leukotriene receptor antagonist, was introduced, and the patient reported an initial improvement in pain. Cromolyn sodium, a mast cell stabilizer, was also added to her treatment regimen to further target her pain exacerbation. Finally, an anti-inflammatory focused GI regimen including betaine HCl, quercetin with bromelain, and other digestive enzymes was trialed. Her progress was monitored using a pain scale over the next six months. However, due to declining health, a subjective narrative scoring system replaced the Visual Analog Scale to represent her fluctuating and multifaceted symptom experience better. The relationship between hEDS, MCAS, and CRPS suggests a multifactorial pathogenesis involving connective tissue fragility, mast cell dysregulation, and neurogenic inflammation. Montelukast, cromolyn sodium, and GI supplementation represent potential therapeutic interventions for managing patients with CRPS linked to MCAS. These treatments offer a novel approach by targeting mast cell-mediated inflammation. This case emphasizes the need for further research into the role of mast cell stabilization in CRPS treatment to improve patient outcomes.

Keywords: complex regional pain syndrome (crps); cromolyn sodium; ehlers-danlos syndrome; mast cell activation; montelukast.

Figure 1. Beighton Score of the patient’s symptoms.

Figure 2. Intersect of various related conditions.

MCAS = mast cell activation syndrome; CRPS = chronic regional pain syndrome; POTS = postural orthostatic tachycardia syndrome Reproduced from [12].