Multiple surgical interventions for refractory subcostal pain in hypermobile Ehlers-Danlos syndrome: a case report spanning vascular, skeletal, and nerve entrapment diagnoses

A 48-year-old woman presented in December 2019 with acute pelvic pain. Initial gynecologic and gastroenterological evaluations were unremarkable. Diagnostic laparoscopy performed in March 2020 revealed endometriosis involving the ovaries, bladder, and peritoneum, and laparoscopic excision was undertaken. Because the pain persisted and intensified, she later underwent hysterectomy with bilateral adnexectomy, appendectomy, and inguinal hernia repair in 2020. After these procedures, the pelvic pain resolved, but new bilateral subcostal pain developed, radiating to the flanks, back, and groin. The pain was aggravated by flexion, coughing, stretching, and turning, and was not related to food intake. Before hysterectomy, she had lost 15 kg; afterward, she gained 20 kg. The chronological sequence of diagnoses, interventions, and outcomes is summarized in Figure 1 . Time chart of diagnoses, surgical interventions and their outcomes. In June 2021 the patient underwent a laparoscopic adhesiolysis and umbilical hernia repair. However, this intervention did not resolve her complaints. Persistent subcostal pain prompted further imaging. Computed tomography angiography demonstrated a retro-aortic left renal vein with focal stenosis and pre-stenotic dilatation, consistent with posterior Nutcracker syndrome, as shown in Figure 2 . In March 2022, she underwent median laparotomy with left renal vein transposition to a preaortic position. Despite a patent reconstruction, her pain persisted without meaningful improvement. Posterior NCS (left renal vein compressed between the spine and abdominal aorta, with pre-stenotic dilatation) displayed in axial view and on sagittal reconstruction of CTAG. Subsequent imaging showed compression of the celiac trunk by the median arcuate ligament, with the characteristic hook sign on sagittal computed tomography angiography, as shown in Figure 3 . This supported the diagnosis of median arcuate ligament syndrome. In October 2023, she underwent laparotomy with resection of the median arcuate ligament. Again, no sustained clinical benefit was achieved, and pain persisted more than five months after surgery. MALS (hook sign of the celiac trunk) displayed on sagittal reconstruction of CTAG. During the diagnostic work-up, the patient was evaluated for hypermobile Ehlers-Danlos syndrome and fulfilled the 2017 diagnostic criteria. Findings included generalized joint hypermobility with a Beighton score of at least 5/9, unusually soft skin, mild skin hyperextensibility, bilateral piezogenic papules of the heels, recurrent surgically treated abdominal hernias, atrophic scarring, and chronic pain, without evidence of skin fragility or another defined connective tissue disorder. Molecular genetic testing was initiated to exclude other types of EDS as well as alternative hereditary connective tissue disorders; the results remained pending at the time of writing. With hEDS recognized, the differential diagnosis was broadened to include skeletal and neural causes. Slipping rib syndrome was suspected clinically and confirmed by dynamic ultrasound, which showed hypermobile costal cartilage of the left eighth to tenth ribs, and by three-dimensional computed tomography reconstruction of the chest demonstrating xiphoid deformity and hypermobility of the false ribs, as shown in Figure 4 . In February 2025, the deformed xiphoid process was resected, resulting in temporary relief for approximately two months. In March 2025, she underwent costochondral revision with L-shaped cartilage resection and osteosynthesis of the hypermobile ribs to the seventh rib. Although there was initial improvement, the subcostal pain fully relapsed. 3D reconstructions on CT chest, showing xiphoid process deformity and hypermobile false ribs. In 2026, anterior cutaneous nerve entrapment syndrome was diagnosed on the basis of localized touch-sensitive subcostal pain and a positive Carnett's test. Intercostal nerve blocks were planned as the next therapeutic step. In July 2026 the patient has undergone the first series of intercostal nerve blocks, which provided short-term pain relief. Given this short but positive outcome, another round of blocks was planned for 3 months later. At the time of writing, the patient was waiting for this second round of blocks to take place.

Hypermobile Ehlers-Danlos syndrome (hEDS) is the most common EDS subtype and is characterized by generalized joint hypermobility, chronic pain, and connective tissue fragility. According to the 2017 international diagnostic criteria, hEDS is diagnosed clinically on the basis of generalized hypermobility (Beighton score ≥5), systemic features (such as hernias, striae, and pelvic organ prolapse), and chronic musculoskeletal pain, after exclusion of other hereditary connective tissue disorders [ 1 ]. Patients with hEDS frequently present with complex, refractory abdominal, subcostal, and pelvic pain. Biomechanical laxity predisposes them to a spectrum of overlapping mechanical problems, including abdominal vascular compression syndromes (AVCS) such as Nutcracker syndrome and Median arcuate ligament syndrome (MALS), skeletal instabilities such as Slipping rib syndrome (SRS), and peripheral nerve entrapments such as Anterior cutaneous nerve entrapment syndrome (ACNES) [ 1 , 2 ]. These conditions often coexist, share non-specific symptoms, and lack universally accepted diagnostic and treatment criteria, which contributes to misdiagnosis and repeated invasive interventions [ 3 - 7 ]. In hEDS, surgical outcomes are generally poorer than in the non-hypermobile population, with higher risks of recurrence, complications related to tissue fragility, and persistent pain despite technically successful procedures [ 8 , 9 ]. Current guidelines therefore recommend conservative, multidisciplinary management as first-line therapy, reserving surgery for carefully selected cases with clearly dominant compressions or instabilities [ 10 , 11 ]. We present a case of a woman with clinically diagnosed hEDS who underwent multiple surgeries for suspected AVCS, SRS, xiphoid deformity, and ACNES, with only transient or no lasting relief. This case illustrates the diagnostic and therapeutic challenges of refractory subcostal pain in hEDS and highlights the need for early recognition of connective tissue disorders to prevent repeated surgical interventions, which fail to provide sustained symptom relief.

This case illustrates how hypermobile Ehlers-Danlos syndrome (hEDS) may be associated with overlapping vascular, skeletal, and neural pain generators, while also limiting the durability of anatomically targeted surgical interventions. The patient's course is consistent with the “multi-compression” and “multi-entrapment” phenotype described in hEDS/HSD, in which abdominal vascular compression syndromes may coexist with abdominal wall weakness, hernias, and nerve entrapment syndromes. Sandmann et al. reported a high prevalence of hEDS/HSD among patients with multiple retroperitoneal and pelvic compression syndromes, together with a high rate of recurrence after decompressive surgery, supporting the concept that connective tissue laxity may predispose both to syndrome development and to postoperative failure [ 4 ]. In our patient, repeated interventions for posterior Nutcracker syndrome, MALS, xiphoid deformity, and slipping rib syndrome resulted in only transient or no lasting relief. A major lesson from this case is that static imaging findings should be interpreted cautiously in a dynamic hypermobile phenotype [ 4 ]. In hEDS/HSD, vessel caliber, anatomical angles, and rib position may vary with posture, respiration, and muscle tone, so positive imaging findings may not always identify the dominant pain generator [ 3 ]. Dynamic or positional assessment, including dynamic rib ultrasound, 3D reconstruction, and focused bedside examination such as Carnett's test, may therefore be particularly valuable [ 12 , 13 ]. Current evidence and hEDS guidance favor conservative, multidisciplinary management before major surgery [ 11 , 14 ]. Clark et al. also showed that patients with hEDS/HSD frequently report variable surgical outcomes and difficult perioperative experiences, underscoring the importance of careful counseling and shared decision-making [ 8 ].

This case highlights the importance of recognizing hypermobile Ehlers-Danlos syndrome (hEDS) in patients with refractory subcostal, flank, or abdominopelvic pain, particularly when imaging shows vascular compression or rib hypermobility. In this patient, multiple plausible pain generators coexisted, including vascular, skeletal, and neural mechanisms, illustrating the complexity of pain assessment in a hypermobile phenotype. The clinical course also shows the limitations of repeated anatomically targeted surgery in hEDS. Despite several technically appropriate interventions, pain relief was only transient or absent. This case supports early hypermobility-aware, multidisciplinary evaluation, with careful clinical examination and dynamic assessment, and suggests that conservative management should be prioritized before further invasive treatment is undertaken. This work was supported by the KEGA grant (No. 050TUKE-4/2022), the APVV grant (APVV-20-0068), and SK-CZ-RD-21-0056. The authors declare no conflict of interest. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.