Unveiling dysplasia epiphysealis hemimelica (Trevor's disease) in the foot and ankle: A systematic review

Abstract

Background

Dysplasia epiphysealis hemimelica is a rare non-inherited condition characterized by the unilateral predominance of osteochondromas in one or more epiphyses, with ankles and knees being the most affected joints. Treatment approaches vary based on the localization of the disease, encompassing both conservative and surgical options. Due to its rarity, there is a lack of definitive surgical guidelines or specific treatment modalities. Therefore, the objective of this systematic review was to thoroughly investigate dysplasia epiphysealis hemimelica to provide evidence-based guidance for managing this condition, specifically focusing on the foot and ankle.

Methods

A systematic search was performed on PubMed and the Cochrane Library to identify all published articles related to dysplasia epiphysealis hemimelica of the foot and ankle. Individual patient information, such as gender, age, disease type, follow-up, localization, clinical presentation, intervention, and complications, were systematically extracted from each article and analyzed.

Results

Twenty-five eligible publications were included in the review, involving a total of 70 patients (16 females, 53 males). The mean age was 9.6 years (SD 7.3). The talus was the most prevalent location and clinical presentations included mass and pain in 54% of cases. Surgical procedures were chosen in 92% of patients, with 95% undergoing mass excision. Recurrence was the most frequent complication, observed in 9% of cases.

Conclusions

Raising awareness about dysplasia epiphysealis hemimelica is crucial for early diagnosis and treatment, positively impacting clinical outcomes. Vigilant monitoring is essential during observational management, as unchecked mass growth can complicate surgical intervention. Surgical treatment focuses on mass excision, feasible even at a young age but requiring precision to prevent recurrence or secondary arthritis.

Level of evidence

IV.

1. Introduction

Dysplasia Epiphysealis Hemimelica (DEH), a rare non-inherited condition, manifests through the anomalous development of one or more epiphyses. It is distinguished by the unilateral predominance of osteochondromas, specifically affecting the medial or lateral side of the epiphysis, hence referred to as ‘hemimelic'.¹ Across its history, this condition has been identified by various names: initially coined ‘tarsomegaly' upon its discovery by Mouchet and Belot in 1926.² Later in 1950, Trevor introduced the term ‘tarsoepiphyseal aclasis' in a case series.³ Fairbank also contributed to its study, ultimately labeling it as DEH, the present identification, alternatively recognized as Trevor's disease.⁴

Trevor's disease presents as a rarity, with an estimated incidence of 1 per million, exhibiting a higher prevalence among males, occurring three times more frequently than in females. No identified genetic or environmental predisposing factors have been linked to its occurrence.⁵

While ankles and knees are commonly affected joints, the condition can also manifest in the hips, feet, upper limbs, and spine. Clinically, Trevor's disease showcases diverse presentations depending on its location, often appearing as a progressively enlarging mass until reaching skeletal maturity. Symptoms usually emerge in early age, enabling diagnosis typically before the age of 15 ⁶.

The suspected diagnosis relies on radiographic examination, following Fairbank's established criteria, indicative of separate ossification centers from the epiphysis with irregular bone growth.⁴ A full diagnostic evaluation through the use of CT (Computerized Tomography) and MRI (Magnetic Resonance Imaging) enables a more detailed description of the lesion, both in terms of morphology and extent.⁷ Confirmation entails histological analysis, achieved through excision of the neoformation, typically displaying as a benign osteochondroma.⁸

The classification of Trevor's disease has undergone several iterations. Initially categorized into three groups by Azouz et al., in 1985, this classification did not encompass all potential cases.⁹ Consequently, a more comprehensive classification was proposed in 2014 by Arealis et al.,⁶ delineating six types based on single or multiple involvement, of the upper and/or lower limbs or the spine.

Treatment approaches vary based on disease localization, encompassing conservative and surgical options.¹⁰ Given its rarity, definitive surgical guidelines or specific treatment modalities are lacking. Therefore, the aim of this systematic review was to comprehensively explore foot and ankle-specific Trevor's disease, aiming to identify optimal intervention timings and methods and to provide evidence-based guidance.

2. Materials and methods

2.1. Search strategy

To systematically review relevant literature for this comprehensive analysis, a structured search was formulated using the PICO framework (Population, Intervention, Comparators, and Outcomes) and following the PRISMA guidelines.

The “Population" of interest encompassed randomized, prospective, retrospective, and observational clinical studies along with case reports that involved patients affected by DEH of the foot and ankle. Within this scope, the “Intervention" focused on various conservative or surgical interventions aimed at managing DEH, particularly emphasizing the timing and methods of treatment. No “Comparators” group was necessary. The “Outcomes” under scrutiny encompassed the principal clinical findings and any associated complications arising from the interventions applied to manage DEH.

A systematic search was conducted on January 6, 2024 across two databases, PubMed and Cochrane Library, to identify all published articles pertaining to DEH of the foot and ankle that included data for each patient involved in the study. For this purpose, combinations of the following keywords were utilized: Trevor's disease; dysplasia epiphysealis hemimelica; tarsomegaly; tarsoepiphyseal aclasis. Exclusion criteria encompassed articles that aggregate data of the included patients rather than presenting them individually for each patient; articles addressing DEH in locations other than the foot or ankle, or presenting results not segregated by localization; articles not written in English; brief communications, letters to the editor, reviews, and meta-analyses. No restrictions were applied based on publication year.

Two reviewers (EA and AM) meticulously assessed the relevance of the identified articles by scrutinizing their titles and abstracts. Any articles not meeting the predetermined inclusion criteria were systematically excluded from this study. Solely those clinical investigations specifically appraising the management of DEH of the foot and ankle were considered for inclusion. To ensure data accuracy, these selected articles were then organized and curated through a publicly accessible reference management system to eradicate any duplicate entries and streamline reference handling.

2.2. Data extraction

The two authors retrieved and reviewed the full-text articles, ensuring thorough scrutiny of the content. Any disparities in assessment were diligently discussed until a consensus was achieved, or if required, referred to the senior author (CF) for resolution.

From each article, individual patient data were extracted. For each patient, the following information was gathered.

• -Authors and publication date;
• -Gender;
• -Age;
• -Disease type in accordance with the Arealis et al. classification⁶: all articles that did not describe additional lesion sites beyond the ankle were classified as type 1;
• -Follow-up;
• -Localization;
• -Clinical presentation;
• -Intervention;
• -Complications.

2.3. Statystical analysis

A comprehensive descriptive analysis was undertaken, wherein categorical variables were presented in terms of percentage, while continuous variables were expressed as mean values with their corresponding standard deviation (SD) or range. The collection of data was executed utilizing Microsoft Excel (Microsoft Corporation, Redmond, WA) designed for Windows 10 operating system.

3. Results

The search of databases returned 422 items in all. Following the removal of duplicates and screening by title, abstract and full-text, 25 publications were deemed eligible for inclusion and were incorporated into the qualitative synthesis.

A total of 70 patients, comprising 16 (23%) females and 53 males (77%) (missing data about sex for one patient), were included in the review. The mean age was 9.6 years (SD 7.3; range, 0.9–45). Among these, 54 patients exhibited type 1 DEH, while 16 patients exhibited type 2 (Table 1).

Table 1.

Data on included patients; NA: not applicable.

AUTHOR	SEX	AGE (YEARS)	TYPE	FOLLOW UP (MONTHS)	LOCALIZATION	CLINICAL PRESENTATION	INTERVENTION	COMPLICATIONS
Arealis; 2014	M	8	1	36	lateral distal tibia	limited ROM, anatomic deformity	excision	recurrence
Gokkus; 2017	M	23	1	2	anterior distal tibia	ankle pain and a limp	arthroscopic excision	–
	M	13	1	9	anterior distal tibia	pain and bony mass	excision	–
	M	12	1		retrocalcanear	pain and bony mass	refused surgery	no
	M	4	2		posteromedial ankle	limping, deformity, limb-lenght discrepancy	excision
Gopinathan; 2013	F	4	1		medial malleolus and talus	acute ankle pain, erythema and swelling	excision
Freihaut; 2007	M	18	1	9	talus	ankle pain	excision + microfractures
Douira-Khomsi; 2011	F	11	1		II metatarsus	protuberance, increasing swelling and pain	excision
	M	15	1		talus and distal tibia	ankle pain	excision + corrective osteotomy
	M	13	1		talus	painless swelling medial ankle	excision
LaBarge; 2023	F	7,1	1	43	great toe	pain	excision	–
	F	5,8	1	2	great toe	pain, mass	excision	pin site infection
	M	9,8	1	44	talus	pain, mass	arthroscopic and open excision	–
	M	1,8	2	132	talus	mass	excision + percutaneus tendo-achilles lenghtening	–
	M	8,8	1	54	talus	mass	excision	–
	M	20,80	1	39	talus	mechanical	tibial fibular osteotomy + Taylor spatial frames	surgical site infection
	M	4	1	2	talus	pain, mass	excision	–
	M	3,3	1	6	distal tibia	mass	–	–
	M	6,3	1	0	distal tibia	pain, mass	–	–
	M	9,5	2	11	talus	pain, mass	arthroscopic and open excision	–
	M	8,8	2	6	talus	pain, mass	arthroscopic excision	–
	M	2,6	1	14	distal tibia	pain, mass	excision	–
	M	14,5	2	43	talus	pain, mass	excision + talonavicolar fusion	–
	F	8,8	2	103	talus	pain	excision	recurrence
	F	1,5	1	130	distal tibia	deformity	tibial internal rotation osteotomy	–
	F	11	1	41	talus	pain	excision	recurrence
	M	3,4	2	50	talus	pain	excision	–
	M	6,77	1	15	calcaneus	pain	–	–
	F	1,3	1	39	distal tibia	mass	–	–
	M	11,8	2	37	talus	deformity	excision	–
	M	4,2	1	88	distal tibia	deformity	excision	–
	F	16,2	1		distal tibia	mass	–	–
	M	13	–	48	talus	pain, mass	excision	–
Dhillon; 2022	M	9	1	8	talus and distal tibia	painful swelling	excision	–
Koshire; 2022	M	8	1	3	medial distal tibial and talus	painful swelling	excision + chemical curettage with phenol	–
Zhang; 2021	M	6	1	12	anterior distal tibia	toe walking	excision	–
Ionescu; 2021	M	8	1		posteromedial ankle	painful deformity and a limp	excision	–
	–	8	1		lateral talus	ankle deformity	observation	NA
Sato; 2021	M	7	1	16	talus	increasing mass and pain	excision	recurrence
Shahcheraghi; 2020	M	8	2		talus and distal tibia	mass and limitation of motion	medial distal tibial growth plate	–
Fetih; 2019	M	6	1	2	anterior and posterior talus	pain and swelling	anterior and posterior arthroscopic excision + microfracture	–
Uygur; 2018	M	6	1	12	talus and distal tibia	ankle pain	excision of impinging lesions	–
Calderaro; 2017	M	9	1	60	talus	ankle pain	posterior arthroscopic and anterior open excision	–
	M	10	1	60	anteromedial talus	pain and swelling	arthroscopic excision	–
Ozan; 2016	F	9	1	14	distal tibia	pain and swelling	excision	–
Papamerkouriou; 2015	M	11	1	36	distal tibia	pain after running and limitation of motion	excision	recurrence
Sadeghifar; 2014	F	21	1	36	anterolateral talar neck	ankle pain and a limp	excision	–
Baumfeld; 2014	F	12	1	144	talar head	medial foot and ankle pain during recreational activities	excision + talonavicular arthrodesis	–
Ouyang; 2014	M	3	1	12	talus and distal tibia	enlarging mass	excision	–
Satija; 2013	M	18	1	9	posteromedial talus	pain, swelling and posterior impingment	excision	–
Trevor; 1950	M	10	1		talus, calcaneus	swelling, limitation of motion	excision
	M	4,5	2	180	medial malleolus and talus	valgus deformity	excision
	M	7	2	42	medial malleolus	valgus deformity	conservative: valgus heel wedge
	M	3	2	–	tibia, talus, navicular, cuneiform	valgus deformity	conservative: valgus heel wedge
Bahk; 2010	F	4	1	72	distal tibia	mass	excision	–
	M	3	1	72	talus	mass	excision	–
	M	2	1	36	talus	mass	excision	–
	F	0,9	2	24	talus, navicular, cuneiforms	deformity	observation
	M	8	2	12	tibia, talus, navicular, cuneiform	mass	excision	–
Rosero; 2007	M	6	1	12	medial talus	painless swelling	excision	–
Kettelkamp; 1966	M	3	1	72	tibia, talus	progressive equinus	conservative for 6 years, then excision	no subtalar motion
	F	11	1	12	lateral talus	increasing mass	excision	–
	M	15	1	24	talus	progressive pain and limitation of motion	partial excision	residual restriction of motion
	M	5,5	2	72	tibia, talus, navicular, cuneiform	ankle deformity	conservative
	M	11	1	0,5	anterior distal tibia	discomfort	excision	–
	M	4	2	24	tibia, talus, navicular, cuneiform	ankle deformity	conservative
	M	28	1	132	posterolateral distal tibia	mass	excision
	M	31	1	108	lateral ankle	enlarging mass	excision	–
	F	45	1	372	calcaneus	mass and pain	excision
Azzoni; 2009	M	8	1	12	talus	painful swelling, impingment	excision	–

In 21% of cases, the lesions were multiple and not attributable to a single joint. Considering all described locations, a clear prevalence was observed at the level of the talus (44 cases), followed by the tibia (32 cases), and to a lesser extent by the navicular (5 cases), cuneiforms (5 cases), and calcaneus (4 cases). Additionally, 2 cases were reported at the great toe, and 1 case at the second metatarsal (Table 1).

Various clinical presentations were reported. The presence of a mass and pain were the most frequent, both occurring in 38 cases (54%). DEH resulted in an evident deformity in 13 cases (19%), encompassing two cases of irreducible equinus. A restricted range of motion with impingement symptoms was identified in 11% of patients. Additional associated symptoms, such as limping, erythema, and lower limb length discrepancy, are delineated in Table 1.

The treatment adopted was detailed for 65 patients. Surgical procedures were selected 92% of the time against 8% of cases receiving conservative treatment. One patient declined surgery.

When evaluating the reported surgical procedures, mass excision was carried out 95% of the time, being performed arthroscopically in 7 of these cases. Other surgical techniques observed included osteotomies, microfractures, talonavicular arthrodesis, Achilles tendon lengthening, Taylor Spatial Frame application, medial distal tibial growth plate procedures, and chemical curettage with phenol. The latter procedures were performed either independently or in conjunction with mass excision. Specifics concerning indications and associated surgical procedures are outlined in Table 1.

Regarding conservative treatment, only Trevor et al. specified their protocol which consisted of a valgus heel wedge. It was also noteworthy that one patient underwent conservative treatment for 6 years before undergoing mass excision.

Data about complications were available for 54 patients. A total of 9 complications were reported (16.7%) at a mean follow-up of 47 months (range, 0.5–372). The most frequent complication was recurrence, occurring in 5 cases (9%), followed by 2 infections and 2 residual movement limitations. No complications were observed in 45 patients (83.3%) (Table 1).

4. Discussion

DEH is a rare condition characterized by abnormal growth in the epiphysis, resulting in unilateral osteochondroma development. The foot and ankle are among the most affected areas, where this pathology can induce deleterious effects causing pain, deformity, limping, and functional limitations.^8,11, 12, 13

This systematic literature review focused on clinical manifestations and treatment of DEH in the foot and ankle district, encompassing types 1, 2, and 5 according to Arealis et al. Given the rarity of type 5 presentations, the included cases predominantly represented types 1 and 2.⁶

DEH typically affects males, with a 3:1 male-to-female ratio,¹⁰ a trend mirrored in the foot and ankle district. Due to the superficial nature of this district, detecting a mass was easily feasible even in early stages. In fact, treatment was predominantly started before the age of 14, with few cases manifesting in adulthood (Fig. 1).

Fig. 1.

Absolute frequency of included patients' ages.

The primary clinical manifestation of DEH was an enlarging mass, variably associated with pain or being asymptomatic, contingent upon its location and adjacent structures. Though typically slow and progressive, sudden growth instances causing acute clinical manifestations were reported, leading to potential confounding with infections,¹⁴ free bodies,¹⁵ osteochondral lesions of the talus,⁵ or Salter Harris 3 epiphyseal fractures.¹⁶ Another differential diagnosis included anterior and posterior impingement due to mechanical restriction from the additional mass.^13,17,18

Radiological imaging differentiated DEH from punctate dysplasia, as the latter involves the entire epiphysis, unlike Trevor's disease, which is hemimelic.¹⁰

Treatment decisions for DEH posed challenges due to the absence of definitive guidelines, neither for timing nor modalities. The treatment was conducted at an average age of 9.6 years. Nevertheless, the decision on when to intervene remains uncertain, with some preferring observation as the mass might be small or asymptomatic at diagnosis; in addition, no malignant transformation of DEH has been reported.^3,10,14,19

However, considering the disease's natural progression until skeletal maturity, a continuous and meticulous observation is essential because future symptomatic development might necessitate excision.^5,10,19 In fact, it is important to prevent the lesion from leading to a deformity or altering the joint surface. These situations could complicate the intervention, potentially necessitating corrective osteotomies for severe deformities^12,20 or arthrodesis if the joint cartilage is affected.^12,21

Early excision was proposed by other authors to enhance joint congruity.^6,22, 23, 24 Nevertheless, the potential disadvantage linked with early intervention was the likelihood of secondary osteoarthritis or recurrence.^14,25 However, analyzing the average age of recurrent patients (9.2 years) showed no significant deviation from the overall average age of the population (9.6 years). Regardless of the chosen treatment, there is consensus in following the patient until skeletal maturity.^10,21

Concerning treatment modalities, limited data were reported on conservative methods, primarily involving the “wait and see" approach or orthotic treatment with a valgus heel wedge to counteract deformity.³ On the contrary, surgical treatment offered more diverse options. Authors proposed treatment algorithms based on the lesion's extra-articular or intra-articular location.

For extra-articular lesions, excision was suggested. For intra-articular lesions, authors advocated a first arthroscopic evaluation, considering leaving the lesion in place and performing hemiepiphysiodesis or osteotomy to correct deformity if the lesion adapted to the joint surface. Otherwise, excision was recommended if the lesion did not adapt.^8,10 In some intra-articular lesions, a cartilaginous flap was observed, prompting some authors to suggest microfractures.^5,26

Finally, uncommon treatments for DEH included joint prostheses. Cases of shoulder hemiarthroplasty and knee prostheses have been described in adulthood, although joint replacement has not yet been applied to the foot and ankle district.^27,28 However, given the growing prevalence and better outcomes of ankle prostheses,²⁹ it might be a future consideration.

4.1. Limitation

This review aimed to offer evidence-based guidance on managing DEH in the foot and ankle district. However, limited literature quality due to the rarity of DEH resulted in primarily low-level studies like case reports and retrospective case series. The decision to extract individual patient data instead of using already provided means from articles meant to retain as much information as possible and simulate a comprehensive case series, the most extensive in the literature on foot and ankle DEH.

5. Conclusions

In conclusion, it is important to raise awareness about the existence of DEH because early diagnosis and treatment can significantly impact achieving favorable clinical and functional outcomes. Vigilant monitoring in observational management of lesions is crucial, as mass growth can deteriorate the clinical condition, rendering surgical intervention more complex and invasive. Surgical treatment predominantly revolves around mass excision, feasible even at a young age, yet requiring precise execution to prevent recurrence or secondary arthritis.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical statement

Institutional Review Board Statement:

Ethical review and approval were waived for this study because it is a systematic review.

Informed consent statement

Patient consent was waived because it is a systematic review.

CRediT authorship contribution statement

Elena Artioli: Methodology, Writing – original draft. Antonio Mazzotti: Conceptualization, Methodology. Maurizio De Pellegrin: Conceptualization, Supervision. Alberto Arceri: Data curation, Writing – original draft. Simone Ottavio Zielli: MD, Writing – review & editing. Laura Langone: Writing – review & editing. Cesare Faldini: Supervision.

Declarations of competing interest

None.