Case Report: Late onset of generalized isomorphic morphea in a postmenopausal woman

Background

Morphea is a rare, sclerosing inflammatory condition of the skin that can involve underlying soft tissues and cause a severe cosmetic and functional defect of unknown etiology. Associated factors, such as genetic predisposition, immune dysregulation, and environmental factors, have been reported^1,2. The current classification includes five subtypes: circumscribed, generalized, linear, pan-sclerotic, and mixed (Table 1)^3,4. Generalized morphea has two patterns of cutaneous distribution, symmetric distribution and isomorphic distribution, which occurs almost exclusively in postmenopausal patients^5,6. The annual incidence ranges between 3.4 and 27 cases per 1,000,000 people, and is more frequent in women than men. This disease has a peak of bimodal incidence, with the age of presentation being between 7 and 11 years in children and 44 and 47 years in adults^7,8.

Case presentation

Clinical findings

The clinical episode began four years ago, starting with indurated, painless skin lesions without erythema in the breast folds, which progressively increased locally. These lesions appeared in other regions, such as the hip and upper and lower extremities, presenting plaques with indurated hiccups and hyperpigmentation (Figure 1–Figure 3). The patient was diagnosed with morphea following clinical examination and a prior pathological biopsy, which reported morphea, in Sweden. A timeline of care is available in Figure 4.

Figure 1. Inactive lesion in left forearm.

Figure 2. Inactive lesion at the level of the right iliac crest.

Figure 3. Inactive lesion at the level of the left iliac crest.

Figure 4. Timeline of care.

Discussion

Morphea is a rare disease, with an estimated incidence of 27 cases per million people. It is suggested that it has an autoimmune origin. In relation to pathophysiology, little is known until now. However, some risk factors have been proposed, the most reported being: trauma, radiation, Borrelia burgdorferri infection, and certain medications^9,10. The age of presentation of this disease in childhood and adulthood, is the age range of 4–62 years, with a mean age of presentation of 35–37 years; in addition, it is more frequent in women than in men, with a ratio of 3:1.^9,11. The presentation is characterized by erythematous or violaceous skin lesions, with the progression of the disease sclerotic plaques develop in the center of these lesions. In some patients, one of the predominant characteristics is the development of hyperpigmentation, and sclerosis may be limited or absent^7,12. Generalized morphea is characterized by superficial, long, and coalescing plaques in multiple parts of the body. This type of morphea is more common in adults than in children, and sclerosis usually occurs in the trunk, upper and lower limbs, with preservation of the face, hands, and feet^7,13.

Regarding the complications of this disease, the injuries caused to the skin can generate functional deterioration and limitation of the motility range of the affected area. The disease can also produce arthralgia, edema, and contractures in the extremities. Initially, sclerotic plaques are formed, which after months and years become hypopigmented or hyperpigmented atrophic plaques that manifest as a depressions in the skin^14,15. In patients with compromised dermis, subcutaneous tissue and muscle, squamous cell carcinoma may be formed due to the present of chronic inflammation^16,17.

In many patients, the diagnosis can only be achieved using clinical findings. However, some imaging studies such as ultrasound, 2-D shear wave elastography and magnetic resonance imaging would be useful in assessing and quantifying morphea extension. In other and histopathological changes, such as compromised dermis, subcutaneous tissue and muscle, may be useful to confirm the diagnosis and evaluate the extent of the disease. Skin biopsy can provide additional information in those patients where the physical examination is inconclusive, also allows us to have information on the depth of the condition and the activity of the disease. Walker et al. assessed a cohort of 83 adults and children with morphea, where they sought to systematize morphological changes and determine the association between histopathological and clinical findings¹⁸. In total, 91 biopsies were performed in 83 patients, and they found three patterns of dermis involvement: superficial, deep, and total sclerosis, which can occur in the different morphea subtypes. For example, in the generalized symmetric morphea, a pattern of deep affection of the dermis predominates; in the generalized isomorphic morphea, a pattern of superficial affection is often presented; on the other hand, lichen sclerosis morphea involves a pattern of linear and superficial affection. In this case, after having carried out a detailed study, skin biopsy was performed, which confirmed the diagnosis of morphea¹⁸.

Dharamsi et al.¹⁹ conducted a cohort study of 181 patients vs controls with the objective of determining the prevalence of antinuclear antibodies, anti-histone antibodies and anti-single-strand DNA antibodies finding that the prevalence of morphea is 34% antinuclear antibodies, 12% anti-histone antibodies and 8% anti-single-strand DNA antibodies. Concerning the patient discussed in this case study, we did not have the results of autoantibodies, so it is not possible to stratify it in any of the groups mentioned above.

The differential diagnosis for morphea is usually systemic sclerosis, this being a systemic disease characterized by progressive dermal sclerosis with the involvement of internal organs. The typical cutaneous manifestations are evidenced symmetrically at the proximal level, presenting as sclerodactyly, Raynaud’s syndrome, facial, trunk and/or limb sclerosis with significant functional limitation, sometimes accompanied by pulmonary and cardiac involvement. Regarding the patient, the condition was exclusively cutaneous without systemic manifestations and without compromising the proximal part of the hands, as happens in systemic sclerosis, also taking into account that the condition is currently in remission without treatment²⁰.

It should be taken into account that the patient was previously diagnosed and had received treatment in Sweden. The patient therefore had access to an advanced health system and did not encounter present economic limitations; it was possible to have timely diagnosis and treatment, which positively affected prognosis. However, within the limitations of the study, it was not possible to have access to the patient’s complete medical history; only the information provided adequately by the patient was used. At present, there are various treatment options for active lesions in generalized morphea, whether superficial or deep²¹. Concerning superficial lesions, it is possible to initially use phototherapy as the first line of treatment throughout the body²². If phototherapy is ineffective, a systemic treatment that includes methotrexate or mycophenolate, alongside systemic glucocorticoids, should be used²³. If the lesions are deep, immediate use of systemic treatment is recommended and phototherapy should be avoided due to poor penetration of ultraviolet light in the deep tissues²⁴. There is also topical therapy in which corticosteroids, vitamin D, and tacrolimus are used. However, it has not proven to be useful in cases of generalized morphea²⁵.

Conclusions

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

Consent

Written informed consent for publication of their clinical details and clinical images were obtained from the patient.