Clinical characteristics and treatment of Morbihan disease of the eyelids: A single-center retrospective study

Abstract

Purpose:

To evaluate clinical and histopathological characteristics and treatment outcomes of Morbihan disease (MD) of eyelids, a rare condition characterized by chronic erythematous edema.

Design:

Retrospective study.

Methods:

Clinical records of patients diagnosed with eyelid and facial MD were reviewed to assess clinical features, treatment outcomes, recurrence, and histopathological findings. Nonsurgical treatments were categorized as observation, oral steroids (oral group), intralesional steroid injections (injection group), and combination group. Treatment response was classified as complete (CR), partial (PR), or no response. Intralesional injections were subdivided into low-dose (<20 mg) and high-dose (≥20 mg). Recurrence was defined as erythematous edema reappearing after CR.

Results:

The study included 67 patients (mean age, 54.3 ± 11.9 years; 65.7% male) with a mean follow-up of 1.69 ± 1.83 years. Of 57 patients who underwent nonsurgical treatments, significant differences in treatment response were observed among oral (n = 13), injection (n = 16), and combination (n = 28) groups (P < 0.001). Injection (56.2%) and combination (64.2%) groups showed higher response rates (CR or PR) than the oral group (38.4%) (P < 0.05). Recurrence was higher in the oral group (53.3%) than in the injection (26.7%) and combination (20.0%) groups (P = 0.018). High-dose injection showed better response than low-dose (70.8% vs. 50.0%, P = 0.017). Debulking surgery with blepharoplasty was performed in 23 patients (40.4%), with 91.3% achieving long-term control. Common histopathological findings included dermal edema (91.3%) and dilated lymphatic or blood vessels (60.8%).

Conclusions:

Intralesional steroid injections, particularly at doses ≥20 mg, were more effective than oral steroids in treating eyelid MD. Eyelid debulking surgery is beneficial in refractory or recurrent cases.

Morbihan disease (MD) is a rare chronic condition characterized by persistent erythematous, firm, nonpitting edema, and it predominantly affects the upper two-thirds of the face, including the eyelids, forehead, nose, glabella, and cheeks.[1,2,3] Patients typically do not report significant pain or pruritus,[2,3,4] but facial disfigurement and visual field narrowing can result in considerable psychosocial discomfort and reduced quality of life.[5] The differential diagnosis of chronic solid eyelid edema includes various conditions such as angioedema, Melkersson–Rosenthal syndrome, thyroid eye disease, chronic contact dermatitis, dermatomyositis, sarcoidosis, systemic lupus erythematosus, and facial granuloma.[6,7] The accurate diagnosis of MD can be challenging owing to overlapping clinical features and the nonspecific nature of laboratory and histological findings.

The pathogenesis of MD remains unclear, although some studies have suggested a link to acne or rosacea, which can lead to the destruction of supporting connective tissue around lymphatic vessels and result in lymphatic dysregulation, obstruction, and chronic inflammation.[3,4] Histopathological analyses have been limited to a small number of cases and typically report nonspecific findings, including dilated blood vessels, stromal edema, and perivascular or perifollicular infiltration by lymphocytes, histiocytes, and mast cells.[3,4,8]

Various therapeutic strategies have been attempted, including systemic agents (e.g., antibiotics, antihistamines, corticosteroids, isotretinoin),[9] intralesional injections, surgical debulking, and combination therapies.[10] Despite these efforts, treatment responses are often suboptimal or temporary, and there are no established consensus guidelines for management. Moreover, the existing literature is largely limited to small case series, and few studies have systematically evaluated recurrence rates or clinical outcomes, particularly in cases involving eyelids from an ophthalmologic perspective.

Therefore, in this study, we aimed to investigate clinical and pathological features of MD involving the eyelids, assess treatment outcomes, and explore recurrence patterns. Our objective was to contribute to the development of evidence-based guidelines for the management of MD involving the eyelids.

Methods

We conducted a retrospective review of consecutive patients who were clinically diagnosed with MD involving the eyelids between June 2016 and December 2022 at the Department of Ophthalmology of a tertiary referral center. This study was approved by the Institutional Review Board (IRB) of Asan Medical Center (IRB No 2023-0943), and written informed consent was obtained from all patients in accordance with the Declaration of Helsinki.

Study design and participants selection

MD was diagnosed based on the characteristic clinical presentation while excluding other differential diagnoses based on patient history, physical examination results, and relevant laboratory test results. Data collected from medical records included demographics (age at initial presentation, sex, presence of systemic diseases), clinical characteristics (laterality, symptom duration, symptoms, signs, anatomical location, and pattern of involvement), radiologic and histopathologic findings, ophthalmologic evaluations, and treatment details (approach, response, and recurrence). Patients were excluded if they had fewer than 6 months of follow-up after treatment or if they had received long-term treatment (≥3 months) elsewhere prior to presentation to our institution. Additionally, exclusions included systemic conditions that could confound the diagnosis, such as autoimmune disorders, severe renal impairment, or uncontrolled diabetes, as well as local conditions in the area under study, including local skin infections (e.g., cellulitis), contact dermatitis, or allergic dermatitis. No randomization or masking was performed in this retrospective study.

Treatment approaches were categorized into four groups: observation without treatment (observation group), oral steroids (oral group), intralesional steroid injections (injection group), or oral steroids and intralesional steroid injections (combination group). Patients in the observation group received conservative management, including warm massage, topical eye drops, and instructions to avoid local irritation; in some cases, patients declined treatment despite medical advice. The protocols for treatments used in this study were developed based on our clinical experience in managing patients with MD. The oral steroid regimen included prednisolone 30 mg/day for 1 week, followed by tapering by 5 mg per week. Intralesional steroid injections (4 mg/0.1 ml; TRIAM®; Shinpoong, Seoul, Korea) were administered trascutaneously to the eyelids using a 26-gauge needle, with the administration of 4–12 mg per site, totaling either <20 mg (low-dose subgroup) or ≥20 mg (high-dose subgroup). Typically, three injection sites (medial, center, and lateral) were used per eyelid depending on the extent of edema, with approximately 4–12 mg administered per site. The injections were spaced evenly across the area of maximal swelling, and care was taken to remain within the preseptal plane while avoiding the globe and major vascular structures. Treatment response was assessed at 4 weeks post initiation of therapy. Repeat injections at 4-week intervals were conducted on the basis of the clinical response and persistence of symptoms. The combination group followed both protocols concurrently.

The primary outcome measures were treatment response and recurrence. Treatment response was evaluated 1 month post-treatment and classified into three categories: complete response (CR), partial response (PR), and no response. The reduction in erythema and edema was classified using a subjective clinical grading scale ranging from 0 to 4 based on the severity of the clinical manifestation.[11]

CR was defined as mild or no erythema (0–2 score), high satisfaction, and ≥80% reduction in eyelid edema. PR was defined as moderate erythema (3 score), satisfactory improvement, and 30–80% reduction in edema. No response was defined as severe erythema (4 score), dissatisfaction, and <30% reduction in edema. A favorable response to nonsurgical treatments was defined as CR or PR. Recurrence was defined as repeated episodes of disease after a minimum sustained remission period of 6 months following the achievement of CR; recurrence-free survival was calculated from the start of treatment to recurrence. Additional nonsurgical treatment was administered in cases requiring the further reduction of eyelid edema or management of recurrent symptoms. If the condition remained refractory to nonsurgical interventions, surgical debulking of the eyelids combined with blepharoplasty was subsequently performed.

Data analysis

Quantitative variables were reported as mean ± standard deviation (SD). Statistical analyses were conducted using SPSS version 23.0 (SPSS Inc., Chicago, Illinois, USA). Categorical variables were compared using the Chi-squared test or Fisher’s exact test for proportions. Continuous variables were analyzed using the independent two-sample t-test or Mann–Whitney U test. Treatment outcomes among the three groups were compared using Chi-square tests for categorical data and analysis of variance for continuous variables. Statistical significance was determined as P < 0.05.

Results

Demographic and clinical characteristics of patients with MD involving the eyelids are summarized in Table 1. In total, 67 patients were included in the study. The mean age of patients was 54.3 ± 11.9 years, and most patients (65.7%) were male. The average follow-up period was 1.69 ± 1.83 years. Among the included patients, 24 (35.8%) had hypertension, 20 (29.9%) had diabetes mellitus, and 24 (35.8%) had dyslipidemia. Bilateral symptoms were present in 32 of 67 (47.8%) patients. Regarding the anatomical location of the eyelid involvement, 82.1% of cases (n = 55) involved the upper eyelid only, 1.5% (n = 1) involved the lower eyelid only, and 16.5% (n = 11) involved both upper and lower eyelids. The most affected facial site was the cheek (n = 39, 58.2%), followed by the nose (n = 19, 28.3%), glabella (n = 17, 25.3%), and forehead (n = 10, 14.9%). Symptoms and signs at diagnosis were erythematous swelling (n = 67, 100%), a sign of rosacea (n = 29, 43.3%), and telangiectasia (n = 26, 38.8%). All laboratory test results were within normal limits, including the assessment of inflammatory markers, autoimmune markers, thyroid markers, angiotensin-converting enzyme, antinuclear antibody, immunoglobulin (Ig) E levels, and IgG4 subclass markers.

Table 1.

Clinical features of 67 patients with Morbihan disease

Characteristic				n=67
Age at diagnosis, mean±SD, years				54.3±11.9
Sex (male: female)				44: 23
Disease duration, mean, years				2.53±2.97
Bilaterality (%)				32 (47.8%)
Habitual alcohol consumption, n (%)				15 (22.4%)
Smoking, n (%)				13 (19.4%)
Eyelid involvement, n (%)		Upper eyelid		66 (98.6%)
		Lower eyelid		12 (18.0%)
Facial involvement, n (%)		Cheek		39 (58.2%)
		Nose		19 (28.3%)
		Glabella		17 (25.3%)
		Forehead		8 (11.9%)
Symptoms and signs, n (%)		Erythematous swelling		67 (100%)
		Signs of rosacea		29 (43.3%)
		Telangiectasia		26 (38.8%)
		Urticaria		11 (16.4%)
		Papule or pustule		1 (1.5%)
Systemic disease, n (%)		Hypertension		24 (35.8%)
		Dyslipidemia		24 (35.8%)
		Diabetes mellitus		20 (29.9%)
		Allergic disease		10 (14.9%)
		Rheumatologic disease		4 (6.0%)

Sixty-seven patients initially enrolled in the study. Of these, 10 patients belonged to the observation group and were excluded from the analysis of treatment outcomes [Fig. 1]. Of 57 patients receiving nonsurgical treatments, 13 (22.8%) received oral steroids (oral group), 16 (28.1%) received intralesional steroid injections (injection group), and 28 (49.1%) underwent combination treatment (combination group) [Fig. 1]. The mean time between the onset of first symptoms and the start of treatment was 30.36 ± 35.64 (range: 6–120) months. Among the three groups, there were no significant differences in the follow-up time after initial treatment and in clinical features including eyelid involvement, symptoms, and signs [Fig. 1]. The median oral steroid dose was 0.86 ± 1.27 (range: 0.74–4.50) g, and the median duration was 3.54 (range: 1.5–45) months. The median steroid dose per intralesional injection was 20.36 ± 11.6 (range: 8–80) mg, and the duration was 2.37 (range: 1–4) months with monthly injections. No patients experienced severe complications associated with oral steroids or intralesional injections, except for two patients who experienced GI symptoms following oral steroids and four patients who had transient elevation of intraocular pressure.

Figure 1.

Overview of the treatment received for Morbihan disease in the study cohort

Treatment outcomes in the oral, injection, and combination groups are presented in Fig. 2. The response to nonsurgical treatment varied significantly among the three groups (P < 0.001): Favorable outcome (CR or PR) rates were significantly higher in the injection (56.2%) and combination groups (64.2%) than in the oral group (38.4%) (P < 0.001 and P = 0.037, respectively), with no significant difference between the injection and combination groups (P = 0.810) [Fig. 2]. In subgroup analysis according to injection doses, the high-dose injection group (≥20 mg) demonstrated significantly better response rates than the low-dose group (<20 mg) (n = 17/24, 70.8% vs. n = 10/20, 50.0%, P = 0.017). There were 15 patients (n = 15/57, 26.3%) who experienced recurrence of disease, which was significantly more frequent in the oral group (n = 8/13, 61.5%) than in the injection group (n = 4/16, 25.0%) and combination group (n = 3/28, 10.7%) (P = 0.018) [Fig. 2].

Figure 2.

Outcomes of nonsurgical treatment in patients with Morbihan disease. * Comparisons in response (complete response [CR] or partial response [PR]) rates to nonsurgical treatment between the groups

Surgical debulking with blepharoplasty was performed in 23 patients (n = 23/57, 40.4%) who did not respond to nonsurgical treatments or experienced recurrence during follow-up. Among these patients, 21 patients (91.3%) achieved sustained satisfactory outcomes without recurrence, while two (8.7%) experienced recurrence 2 years post surgery and were treated with intralesional injections [Fig. 3]. Histopathologic examinations (n = 23) indicated the presence of dermal edema (91.3%), dilatation of lymphatic or blood vessels (60.8%), lymphocytic infiltration (30.4%), granulomas (17.4%), and other findings such as elastic fiber degeneration, collagen degeneration, or Demodex folliculitis (21.3%).

Figure 3.

(a) A 39-year-old male with chronic erythematous edema of both upper eyelids for 1.5 years. (b) Partial response was observed after intralesional triamcinolone injection (40 mg/1 mL) into each upper eyelid. (c) Complete response was achieved with additional injections (20 mg/0.5 mL) into each upper eyelid and oral steroids (30 mg, with tapering). (d) Recurrence occurred 5 months later, leading to (e) surgical debulking. (f) The patient maintained a sustained favorable outcome without recurrence at the latest follow-up at 1 year postsurgery

Discussion

The findings of the present study, which analyzed the data of a large number of Korean patients from a single center, provide valuable insights into the clinical characteristics and management of MD of the eyelids. Our findings suggest that MD predominantly affects males, with two-thirds of the patients being male, and is typically diagnosed in middle age, around the mid-50s. Furthermore, our studies revealed intriguing patterns of involvement within the affected facial regions. A significantly higher proportion of patients exhibited upper eyelid involvement (98.5%) than those who exhibited lower eyelid involvement (17.9%), with cheek involvement (58.2%) also being notably common. Regarding treatment outcomes, our results suggest that intralesional steroid injections and combination therapies are more effective than oral steroids alone. Surgical debulking is considered a viable treatment option for refractory MD of the eyelids.

Our study presents updated insights into demographic profiles of patients with MD of the eyelids, highlighting a predominance of middle-aged individuals (mean age, 54.3 years), males (65.7%), and those with signs of rosacea (43.3%), with a mean pretreatment disease duration of 2.53 years. The most frequently reported symptoms and clinical signs in our study population included erythematous swelling (100%), signs of rosacea (43.3%), and telangiectasia (38.8%). These results are consistent with those of a previous systematic review including 93 MD cases from 57 studies with various ethnicities,[12] reporting the mean patient age of 49 years; male predominance (69%); affected facial regions of the middle face including the eyelids (73%), cheeks (42%), and forehead (31%); and nonpitting erythematous edema as the most common clinical features.

Of note, the upper eyelid (98.5%) was the area most affected by MD in our study. This may result from the fact that the skin of the upper eyelid is notably thinner and more delicate than the skin of other facial regions, and from its unique lymphatic anatomy, which makes the area vulnerable to swelling when lymphatic flow is impaired. As demonstrated by Nijhawan et al.,[13] the upper eyelid contains a rich, multilayered capillary and lymphatic plexus that drains primarily into both the preauricular and submandibular lymph nodes. Unlike the simpler and more unidirectional lymphatic pathways of the lower face, this complex network may further predispose the upper eyelid to persistent edema under disease conditions. Furthermore, the cheek (58.2%) was the second most frequently affected site on the face in our study. Considering lymphatic dysfunction could be one of the etiologies for MD, the high lymphatic drainage capacity of the cheek, which typically has 3–6 submandibular nodes,[14] may be associated with a predilection for MD in the cheek. However, any conditions that impair lymphatic drainage can lead to edema of the eyelids, cheeks, and other facial regions. Therefore, the clinical features of MD may be nonspecific, highlighting the importance of carefully evaluating these features and excluding other potential causes during the diagnostic process.

MD pathogenesis remains unclear, but damage to lymphatic and blood vessels and subsequent lymphatic stasis and edema are considered the main pathologic findings of MD,[2] as also shown in our cohort. In terms of underlying causes, some studies have suggested increased oxidative stress, which impairs nitric oxide and reactive oxygen species,[15,16,17] or chronic inflammation, which in turn damages lymphatic and blood vessels.[2] In our study, we used steroids for the nonsurgical treatment of MD of the eyelids to address chronic inflammation and subsequent lymphatic impairment as potential etiologies. More than half of the included patients (56%) responded favorably to initial nonsurgical treatment, aligning with the findings of a previous systematic review indicating a response rate of 64% in patients with MD.[12] However, most previous studies reported the use of long-term oral medications such as isotretinoin, tetracycline, ketotifen, and steroids,[12,18,19] with the average medication duration to CR or PR being 157 days.[12] In contrast, our data highlighted the usefulness of intralesional steroid injections for MD of the eyelids, with the response rate of 61.4% (n = 27/44) in the injection and combination groups. Considering the potential complications, cost, and compliance issues associated with long-term oral medication, intralesional injection may represent a simple and effective treatment option for MD. Furthermore, our data indicated that high-dose injections (≥20 mg) are more effective than low-dose injections (71% vs. 50%). This greater efficacy may be attributed to higher local concentrations of anti-inflammatory agents, which are likely more effective in resolving persistent lymphedema and perivascular inflammation than insufficient local delivery.[20]

Although the combination group showed the highest proportion of favorable responses, this should be interpreted cautiously. Treatment patterns shifted over the study period—oral steroids were used predominantly in the earliest phase, combination therapy in the middle phase, and intralesional injections became the primary modality thereafter. Because of this time-dependent evolution in practice, the apparent advantage of the combination group may largely reflect the increasing use and effectiveness of intralesional injections rather than a true additive benefit of oral steroids. The lack of a statistically significant difference between the combination and injection-only groups supports this interpretation. A sequential regimen, beginning with oral steroids and reserving intralesional injections for nonresponders, could have offered clearer comparative insight; however, this was not feasible within the retrospective and evolving clinical context of our institution. Future prospective studies with structured, sequential, or stratified treatment arms will be important to clarify the relative contribution of each modality.

In our cohort, the recurrence of swelling was common (26%) after achieving CR with nonsurgical treatments; 40% (n = 23/57) of patients ended up receiving surgical debulking of the remnant or recurrent eyelid swelling. Our data demonstrated that surgical debulking can be effective for salvage treatment for refractory swelling, with 91% patients (n = 21/23) remaining stable after surgery. A previous report demonstrated a case of MD with satisfactory outcomes on lymphaticovenous anastomosis (LVA) to improve lymphatic drainage and blepharoplasty to debulk the enlarged tissue.[21] In our cohort, surgical debulking with blepharoplasty was performed without LVA and still showed sustained satisfactory outcomes. The most common histopathologic features in our cohort (n = 23) included dermal edema and dilatation of lymphatic or blood vessels, followed by lymphocytic infiltration and granulomas. These findings are consistent with those of a previous study with 14 MD cases, which suggested that the histopathology of MD fits within the spectrum of localized lymphedema.[22] Chronic lymphedema often leads to irreversible changes such as fibrosis, granulomatosis, and hyperkeratosis, which are typically unresponsive to nonsurgical treatments and may require surgical excision.[10] In patients over 50 years of age, who are commonly affected by MD, dermatochalasis is common and often worsened by the disease. Furthermore, the affected regions frequently overlap with blepharoplasty sites. Given the functional and psychosocial significance of the eyelids, surgical intervention is a reasonable option in refractory cases. Given the technical difficulty of LVA and our favorable outcomes without it, surgical debulking with blepharoplasty alone appears effective for eyelid involvement in MD.

Our study has several limitations, primarily owing to its retrospective design and relatively modest sample size. Additionally, because the study included only Korean patients, the findings may not be generalizable to other ethnicities. Nevertheless, this study represents one of the largest series of MD, and its single-center nature allows for the more consistent evaluation and comparison of clinical features and outcomes. Second, treatment allocation in this study was not randomized and was influenced by clinical judgment; however, because the predominant treatment modality shifted in a time-dependent manner, the risk of allocation bias may have been partially reduced. Nevertheless, residual confounding remains, and future prospective or randomized studies are needed to more accurately compare treatment efficacy. Third, our approach to the nonsurgical treatment of MD primarily involved the use of systemic oral steroids or intralesional steroid injections to address inflammatory etiologies and subsequent lymphedema. However, there have been alternative systemic treatments, such as antibiotics, isotretinoin, tacrolimus, or doxycycline.[23] Further research is required to compare the effectiveness of other nonsurgical treatments. Fourth, surgical debulking procedures were performed after the application of nonsurgical treatments, which could potentially influence the histopathological findings. Nonetheless, it is notable that these surgical procedures were performed 6 months after the previous treatment, minimizing their potential impact on the study’s results. Finally, although we found that high-dose steroid injections (≥20 mg) and repeated injections depending on patients’ response are recommended, we were not able to formulate an appropriate guideline for injection doses and sessions. A follow-up study is necessary to establish guidelines for nonsurgical treatments.

Conclusion

Intralesional steroid injection, particularly at doses of ≥20 mg, appears to be a safe and effective first-line treatment for MD of the eyelids. For patients with refractory or recurrent cases, surgical debulking with blepharoplasty offers a reliable option for long-term management. These findings may inform future treatment strategies and support the development of standardized clinical guidelines for this challenging condition.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.