Linear morphea distributed along radial nerve with high incidence of neuromusculoskeletal disorders: A single-center case series

Abstract

Linear morphea is the most disabling subtype of morphea, which may cause a series of excutaneous manifestations and sequelae. To futher explore the clinical characteristics of linear morphea, we conducted a retrospective study of 22 patients diagnosed with linear morphea in our department during the past 2 years. Their baseline clinical information, skin manifestations, complications and therapeutic effect were analyzed. Here, we report six cases of a special linear morphea, usually occurring on the unilateral upper limbs of young women, spreading along the distribution of the radial nerve and frequently progressing across the joint, which increases the incidence of neuromusculoskeletal disorders. Instead of traditional topical drugs, a combination of systemic prednisone and methotrexate improved their skin lesions and complications. Recognition of this special type of linear morphea enables earlier diagnosis and active treatment plan, which contributes to ameliorate the symptoms and avoid functional sequelae.

1. Introduction

Morphea, also known as localized scleroderma, is a rare inflammatory disease characterized by sclerosis of the skin and soft tissue, with an incidence of about 0.4–2.7 per 100 000 in the population [1]. Morphea can be divided into plaque, generalized, linear, and mixed types [2]. Although not usually life-threatening and without Raynaud's phenomenon or internal organ involvement, morphea is not limited to skin manifestations. Specifically, linear morphea that is frequently accompanied by neurological and musculoskeletal irregularities has a high rate of disability [3,4].

As most research on linear morphea has been carried out in children and there have been no longitudinal studies to date, the clinical features, standard treatment, and efficacy of therapeutic interventions for linear morphea have not been completely elucidated, thus limiting timely diagnosis and appropriate treatment [5,6]. To address this knowledge gap, the present study included the detailed clinical data with post-treatment follow-up, and showed the characteristics and treatment experience of a special linear morphea distributed along the radial nerve. To our knowledge, few reports about linear morphea with this special location have been published so far.

2. Methods

2.1. Patients

We presented data on clinical information, skin manifestations, therapeutic interventions, and clinical course of 6 patients with skin lesions distributed along the radial nerve form 22 patients diagnosed with linear morphea at Zhongshan Hospital, Fudan University, Shanghai, China, between July 2021 and July 2023.

2.2. The modified localized scleroderma skin severity index (mLoSSI)

The mLoSSI, part of the Localized Scleroderma Assessment Tool, is used to evaluate the activity of the disease [7]. The mLoSSI assesses three domains including new lesion/lesion extension, erythema and skin thickness. The appearance of a new lesion or the enlargement of an existing lesion within the preceding month is assigned a score of 3. Other domains are rated on a distinct 4-point scale ranging from 0 to 3. Elevated mLoSSI scores correlate with increased disease activity.

2.3. Durometer measurement

Durometer was described as a credible tool for the evaluation of skin induration in past single or multi center examinations [[8], [9], [10]]. So, a digital durometer (Rex Gauge type OO; Rex Gauge, Buffalo Grove, IL) with a continuous scale was used in a subpopulation of these patients to assess changes in skin hardness and effects of therapeutic interventions (Fig. 1). The durometer readings were taken at the intersection of two imaginary lines drawn through the largest horizontal and vertical diameters of the lesion. Three consecutive readings were taken from both skin lesions and the normal skin on its contralateral side.

Fig. 1.

Demonstration of the durometer operation.

2.4. Statistical analysis

Chi-square test was adopted for categorical data. A p < 0.05 was regarded as statistical significance. Statistical analysis was performed via GraphPad Prism 7.03 (GraphPad Software, La Jolla, CA, USA).

3. Results

3.1. Case 1

A 20-year-old female patient presented skin lesions located on the right upper limb (Fig. 2A). She was histologically diagnosed with linear morphea three years earlier and had no family history of autoimmune disorders. She reported the lesion initially appeared on the right forearm without accompanying symptoms, and she was managed with topical corticosteroids and oral total glucosides of paeony capsules after diagnosis. The skin lesion did not shrink, but instead progressed toward the right upper arm and dorsal hand gradually. Meanwhile, numbness, pain and cramp appeared in the right upper limb.

Fig. 2.

Skin manifestations of the six patients. (A) Case 1, physical examination showed flat, striped, sclerotic patches with hyperpigmentation on the right dorsal hand, forearm and upper arm along the radial nerve. (B) Case 2, physical examination showed brown, porcelain, swollen, sclerotic lesions surrounded by inflammatory erythema on the right dorsal hand, forearm and upper arm along the right radial nerve. (C) Case 3, physical examination showed broad dark brown sclerotic plaques with orange peel appearance, venous exposure and punctate hypopigmentation on the radial aspect of the right forearm and near the elbow joint. (D) Case 4, physical examination showed dark brown sclerotic patches in the right upper limb along the radial nerve, with obvious tight sclerosis near the elbow and nodular sclerosis palpable under the skin. (E) Case 5, physical examination showed dark red, sclerotic, atrophic patches, with hypopigmentation and hyperpigmentation, on the left forearm near the wrist and at the left elbow. (F) Case 6, physical examination showed shiny, brown, sclerotic patch on the left dorsal hand with venous exposure and brown patches on the left forearm. (G) Schematic diagram of the distribution of the radial nerve. These images demonstrated the high degree of consistency between the lesion alignment and the distribution of the radial nerve in these patients.

We treated her with a systematic treatment including prednisone (20 mg/day, oral) and methotrexate (10 mg/week, oral). Specifically, prednisone was reduced to 15 mg per day after 3 months of treatment, and then further reduced to 10 mg per day after an additional month, with the total therapy duration maintained for 6 months. Methotrexate dosage remained unchanged and aimed to be maintained for 1 year. During the next 7 months of follow-up treatment, the skin lesions became lighter and smaller. The mLoSSI score was lowered from 19 to 3 (Table 1) and the durometer score of lesions reduced (Fig. 3A). The symptoms of numbness and tenderness were relieved, but the patient still reported occasional cramp. Throughout the treatment period, she was regularly monitored for blood routine, blood glucose, electrolytes, blood pressure, and liver function. No adverse events were observed.

Table 1.

Patients’ mLoSSI score of each domain.

Patient No.	Sex	Treatment Duration	Location	Before Treatment			After treatment
				N/E	ER	ST	N/E	ER	ST
1	F	7 months	Dorsal hand	3	1	2	0	0	0
			Forearm	3	2	2	0	1	1
			Upper arm	3	1	2	0	0	1
2	F	7 months	Dorsal hand	3	2	2	0	0	0
			Forearm	3	1	1	0	0	0
			Upper arm	3	2	2	0	1	1
3	M	5 months	Forearm Upper arm	3	1	2	0	0	1
				3	2	3	0	1	2
4	F	7 months	Forearm	3	0	3	0	0	1
			Upper arm	3	3	1	0	1	0
5	F	5 months	Forearm	3	1	2	0	0	1
			Upper arm	3	2	2	0	1	1

mLOSSI: the Modified Localized Scleroderma Skin Severity Index; M/F: male/female.

N/E: New lesion/lesion extension; ER: Erythema; ST: Skin thickness score.

Fig. 3.

The changes of durometer score. The horizontal coordinate was the time the patient received durometer measurement after starting new treatment regimen. The vertical coordinate was the durometer score. Hand, forearm and upper arm were marked in orange, green and blue respectively. The right side was marked with a black dot and the left side was marked with a colored dot. (A), (B), (C), (D), (E) represented case 1, 2, 3, 4, 5 respectively.

3.2. Case 2

A 33-year-old female patient presented with skin lesions located on the right upper limb and dorsal hand (Fig. 2B). Our histopathologic slide was consistent with the diagnosis of morphea (Fig. 4A). She denied family history of autoimmune disorders. She reported the lesion initially appeared on the right forearm one and a half years ago and she ignored the abnormality. Then, the skin lesion progressed across the elbow joint and wrist joint. Besides numbness and pain, she presented limited movement of the right elbow joint.

Fig. 4.

(A) Histopathologic slide of case 2 suggested morphea (hematoxylin–eosin staining, magnification 280-fold). The arrangement of collagen fibers was coarse and dense in the middle to deep dermis. (B) Histopathologic slide of case 3 suggested morphea (hematoxylin–eosin staining, magnification 280-fold). The collagen fibers in the middle to deep dermis and subcutaneous fat interval were thickly proliferated, densely arranged, and the skin appendages were reduced. Inflammatory infiltrate with lymphocytes and a few plasma cells can be seen around the dermal vessels.

She was treated with systematic treatment plan of prednisone (20 mg/day, oral), and methotrexate (7.5 mg/week, oral). Prednisone was similarly reduced to 15 mg per day starting from the 4th month and reduced to 10 mg per day from the 5th month, with a total treatment duration of 6 months. The dosage of methotrexate remained unchanged and aimed to be maintained for 1 year. During the next 7 months of follow-up treatment, the mLoSSI score dropped from 19 to 2 (Table 1) and the durometer score was decreased (Fig. 3B). The symptoms of numbness and pain were alleviated, and the limited joint movement recovered, without functional sequelae left. She was also regularly monitored for blood routine, blood glucose, electrolytes, blood pressure, and liver function. No adverse events were observed.

3.3. Case 3

A 31-year-old male patient presented with sclerotic skin lesions located on the right upper limb (Fig. 2C). Our histopathologic slide suggested the diagnosis of morphea (Fig. 4B). He also denied family history of autoimmune disorders. He reported the lesion initially appeared on the right forearm without accompanying symptoms three months ago. He ignored the skin disorder at first. Then, the skin lesion gradually progressed across the elbow joint to the right upper arm, accompanied by numbness and pain in the right elbow joint.

A systemic treatment of prednisone (20 mg/day, oral) and methotrexate (10 mg/week, oral) was taken with him. Prednisone was also reduced to 15 mg per day beginning in the 4th month and reduced to 10 mg per day from the 5th month. Methotrexate treatment remained unchanged. During the next 5 months of follow-up treatment, the mLoSSI score dropped from 14 to 4 (Table 1). The durometer score was also decreased (Fig. 3C). Moreover, the symptoms of numbness and pain resolved, and no adverse events were observed.

3.4. Case 4

A 21-year-old female patient presented with skin lesions located on the right upper limb (Fig. 2D). She was histologically diagnosed with linear morphea nine years earlier and had no family history of autoimmune disorders. She said the lesion initially appeared on the right forearm without accompanying symptoms and she was managed with systemic corticosteroids after diagnosis. Over the next few years, her lesions improved and she gradually stopped taking the drug. ln the last year, the original lesion on the right upper arm hardened again and extended across the elbow joint to the right upper arm. Meanwhile, this patient presented with limitation of right elbow motion.

She was treated with prednisone (20 mg/day, oral) and methotrexate (7.5 mg/week, oral). Prednisone was reduced by 5 mg each in the 4th and 5th months, maintaining a total duration of 6 months. Methotrexate remained at its initial dosage. During the next 7 months of follow-up treatment, the mLoSSI score dropped from 13 to 2 (Table 1) and the durometer score was decreased (Fig. 3D). Her limited joint movement was recovered, without functional sequelae left. No adverse events were reported throughout the entire follow-up period.

3.5. Case 5

A 24-year-old female patient presented with skin lesions located on the left upper limb (Fig. 2E). She was histologically diagnosed with linear morphea two and a half years earlier, and had no family history of autoimmune disorders. She reported the lesion initially appeared on the left forearm three years ago without any complications and she was managed with topical corticosteroids and oral compound glycyrrhizin capsule after diagnosis. However, she felt concerned the lesions had not improved significantly and a similar lesion had appeared on her left elbow in the last half year.

Although there were no complications, we adopted an aggressive treatment plan of prednisone (10mg/day, oral) and methotrexate (5 mg/week, oral) considering the progression characteristics of her skin lesions. The prednisone treatment aimed to be maintained for 6 months, while the methotrexate treatment aimed to be maintained for 1 year. During the next 5 months of follow-up treatment, the mLoSSI score dropped from 13 to 3 (Table 1), and the durometer score was decreased (Fig. 3E), with no reported adverse events.

3.6. Case 6

A 25-year-old female patient presented with skin lesions located on the left upper limb (Fig. 2F). This patient was histologically diagnosed with linear morphea eight years earlier and had no family history of autoimmune disorders. She reported the lesion initially appeared on the left dorsal hand and she was managed with topical calcineurin inhibitor. She felt that her lesions had recently worsened and that some lesions had appeared on her left forearm.

We adjusted her treatment plan to prednisone (10mg/day, oral) and aimed to be maintained for 6 months. However, she did not follow up with our clinic every month as prescribed by us. Fortunately, during the follow-up phone call after 3 months of treatment, she reported that her lesions were gradually improving, and no complications or adverse events occurred.

4. Discussion

In our series, the male to female ratio was 1:5 and the average onset age was 21.5 ± 7.9 years old. The female predilection of linear morphea is consistent with previous literature [11]. It is worth noting that 66.7 % (4/6) of the patients showed complications such as pain, numbness, cramp and even limited movement of joint. However, in the remaining 16 patients with linear morphea seen in our department during the same time period, there were only 12.5 % (2/16) patients presented with excutaneous manifestations. Patients with the special linear morphea had a high incidence of neuromusculoskeletal disorders (p = 0.011).

Morphea, especially in cases of the linear subtype, are not limited only to the skin but can also involve the neuromusculoskeletal system and, in severe cases, can result in permanent cosmetic and functional sequelae[12,13]. However, the clinical features of morphea lack in-depth generalized analysis, and standard treatment has yet to be defined.

As far as we know, this is the first report to date of the distribution of linear morphea along the radial nerve. In our series, the special linear morphea usually occurs in young women and begins on the radial side. It may be limited to one anatomical site initially, and misdiagnosed as plaque morphea. However, the sclerotic rash progresses insidiously along the radial nerve, which means it tends to develop across the wrist or elbow joint (Fig. 2G). In addition to tension and stiffness, patients commonly show neuromusculoskeletal disorders. Therefore, unlike other types of localized morphea, which generally do not require active treatment and can be treated with topical drugs combined with phototherapy, we recommend more aggressive treatment with a combination of systemic prednisone and methotrexate and closer follow-up for the special linear morphea, which can improve clinical symptoms, inhibit progression, and avoid functional sequelae [14]. Generally, our initial dose of prednisone was approximately 0.5 mg/kg per day, administered orally, with gradual tapering over 6 months. Methotrexate was dosed at about 5–7.5 mg/m² per day, taken orally, and maintained for 1 year. In patients with only skin involvement, the dosage can be reduced.

The serious consequences of linear morphea and the importance of early recognition and systemic immunosuppressive treatment are well known [15]. However, it is often difficult to determine the appropriate timing for aggressive treatment because of the paucity of markers and lack of universal skin activity features. This specific linear morphea provides some insight. Our study also has limitations, including a small sample size, a relatively short follow-up period, and the absence of nerve conduction studies to further confirm radial nerve involvement in patients. Further studies are required to explore the relations between morphea and the central or peripheral nervous system [16].

5. Conclusions

In summary, our study demonstrates a special linear morphea distributed along the radial nerve, predominantly occurring in young females and often progressing across joints, leading to a propensity for neuromusculoskeletal complications. A positive combination therapy of systemic glucocorticoids and methotrexate has been confirmed in our cohort to alleviate disease symptoms and avoid functional sequelae.

Ethics statement

All patients provided written informed consent prior to enrollment in the study for the publication of their anonymised case details and images. The protocol was approved by the Ethics Committee of Zhongshan Hospital, Fudan University. The ethical approval number was Y2021073.

Funding disclosure

This study is supported by National Natural Science Foundation of China (82073436, 82373463).

Data availability statement

The data associated with our study has not been deposited into any publicly available repository. However, the authors grant all external authors access to clinical study data pertinent to the development of their publications. Data and analysis are available from the corresponding author on reasonable request.

CRediT authorship contribution statement

Xiuyuan Wang: Writing – review & editing, Writing – original draft, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Xue Han: Writing – original draft, Methodology, Formal analysis, Data curation. Feifei Hu: Writing – review & editing, Methodology, Data curation. Xinzhi Xu: Writing – review & editing, Data curation, Conceptualization. Junxia Huang: Methodology, Formal analysis, Data curation. Ji Yang: Writing – review & editing, Writing – original draft, Supervision, Project administration, Funding acquisition, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.