Methotrexate for localized morphea with severe pain: A case report
Published Web Locationhttps://doi.org/10.5070/D33c09t6cd
Letter: Methotrexate for localized morphea with severe pain: A case reportDavid Geffen School of Medicine at UCLA, Los Angeles, California
Hana Jeon AB, Christina Kim MD
Dermatology Online Journal 17 (12): 12
Morphea, also known as localized scleroderma, is characterized by idiopathic fibrosis of the skin and adjacent structures. Patients with morphea classically present with skin lesions without any associated symptoms and the lesions usually regress spontaneously over time. We describe a patient with morphea who presented with debilitating pain in her skin plaque. She failed topical therapy and required systemic methotrexate to control her disease. We titrated the methotrexate dose with the goal of pain relief. Although unusual, pain associated with morphea can be debilitating. Physicians should assess for pain in patients with morphea and prescribe treatments accordingly. We propose using pain, when present, in addition to physical examination as a guide for titrating morphea therapy.
|Figure 1. Five mm, violaceous plaque with atrophy and hypopigmentation in the center, on the patient’s posterior right thigh|
A 22-year-old woman presented with a four-year history of plaque-type morphea, on her posterior right thigh. She had been treated with desoximetasone cream and calcipotriene ointment. She presented with daily, severe, burning pain in the area for six months. The pain was exacerbated with pressure, especially while sitting, thus preventing her from working at her desk job. She had no other significant medical history. Review of systems was negative. In particular, she denied photosensitivity, joint pain, and Raynaud phenomenon. On examination a tender, five mm, violaceous plaque was present with atrophy and hypopigmentation in the center (Figure 1). A cliff sign was absent and there was no surface change. The differential diagnosis included morphea, atrophoderma, cutaneous lupus, panniculitis, livedo reticularis, and eosinophilic fasciitis.
A punch biopsy was performed, which revealed an unremarkable epidermis and sclerosis of the superficial and deep dermis characterized by thickened homogeneous collagen bundles and trapping of eccrine glands (Figures 2a and 2b).
There was no significant increase in mucin deposition as noted with colloidal iron and Alcian blue stains. These findings were consistent with morphea. Laboratory evaluation included serology for anti-nuclear antibody, anti-double stranded DNA, anti-SSA, anti-SSB, and lyme titers, which were all within normal limits. Complete blood count was normal. An MRI was performed to evaluate for eosinophilic fasciitis. There was no evidence of deep tissue inflammation on the MRI. With these histological findings, negative laboratory and imaging evaluations, and the clinical picture of an isolated lesion, a diagnosis of localized morphea was rendered.
Initial therapy included ultrapotent topical steroids in combination with calcipotriene cream. However, the patient continued to experience severe tenderness in the area, preventing her from driving or sitting down. This rendered her incapable of working. During the course of two weeks, the white atrophic plaque with a violaceous border rapidly enlarged from the size of 10 x 8 cm to 12 x 15 cm, with increased erythema and induration. The patient was treated with oral prednisone 40 mg daily for one week. The dose was tapered down over the course of two weeks. Her topical therapy was changed to tacrolimus 0.1 percent ointment twice daily. On physical examination, the large indurated plaque improved and became smaller, white, and atrophic. However, the patient continued to experience severe pain.
Because of the pain, the patient was started on methotrexate. The dose of methotrexate was titrated up with weekly complete blood count and liver function tests. She reached a stable dose of 10 mg per week, with no significant gastrointestinal discomfort and no laboratory abnormalities. She continued to use topical tacrolimus ointment as well, with intermittent use of topical lidocaine. She was also advised to take 1 mg of folate supplementation.
Following one month of this therapy, she reported improvement in pain and tenderness in the area. On physical examination, she had an atrophic patch with erythema surrounding it. She continued to improve such that she experienced minimal pain and had no adverse effects from her therapy. She did suffer a flare of her disease, with recurrence of pain at the site, after eight months. Interestingly, physical examination remained largely unchanged and showed a persistent atrophic white plaque. Her dose of methotrexate was increased to 12.5 mg weekly. This was tapered down once her pain improved and she was back to 10 mg of weekly methotrexate after two months. She was eventually able to return to work.
Morphea, also known as localized scleroderma, is characterized by idiopathic fibrosis of the skin and adjacent structures. Unlike systemic sclerosis, morphea does not involve internal organs and has a good long-term prognosis . Cutaneous findings also differentiate morphea from systemic sclerosis by the absence of sclerodactyly, perioral involvement, or periungual telangiectasias . It is estimated that the prevalence of morphea is roughly 27 cases per million, with whites slightly more often affected than non-whites .
The pathophysiology of morphea remains largely unknown. Although it is thought that dermal fibroblasts overproduce collagen and glycosaminoglycans, thereby resulting in morphea, the etiology behind this aberrant activity is unknown. Some of the possible mechanisms include autoimmune dysregulation and abnormal cytokine production. Medications, chemicals, malignancies, and radiation therapy are possible environmental triggers that might contribute to the onset of morphea [1, 3].
Morphea can be categorized into the following subtypes depending on clinical presentations: plaque type, generalized, bullous, linear, and deep. Plaque and generalized morphea usually have an insidious onset and affect the trunk . Plaque morphea typically begins as a patch of erythema or edema and becomes indurated, which can then result in atrophy, depigmentation, or hyperpigmentation upon resolution . Generalized morphea is a more severe form of plaque morphea that is characterized by multiple lesions or coalescence of individual plaques. Bullous morphea is characterized by vesicles in plaques of morphea that may be on the trunk, extremities, face, or neck. Linear morphea is usually unilateral, affects an extremity, and consists of linear indurations that may extend into the muscle and bone. Such deeper involvement can result in severe limb atrophy and contractures . Deep morphea is similar in that it affects deep structures such as deep dermis, subcutaneous tissue, or superficial muscle, but it presents diffusely rather than linearly .
Because there is not a specific, confirmatory test, the diagnosis of morphea is made clinically and histopathologically . Histopathologic findings help to exclude other fibrosing disorders from morphea, which include drug reaction, mycosis fungoides, scleromyxedema, myxedema, scar, radiation dermatitis, amyloidosis, chronic graft-versus-host disease, lipodystrophy, sarcoidosis, and nephrogenic systemic fibrosis . Laboratory abnormalities may provide clues in diagnosing morphea. Eosinophilia has been reported in patients with generalized or linear morphea , and circulating antibodies such as antinuclear antibodies, anti-single-stranded DNA antibodies, and antihistone antibodies have been reported in morphea . Localized morphea, however, is usually absent any laboratory findings.
Once the diagnosis of morphea is made, there are several ways to manage the disease. In addition to reassuring the patient that it is benign and often self-limited, topical agents (e.g., corticosteroids, calcipotriene), phototherapy (i.e., UVA-1), or systemic therapy (e.g., methotrexate, vitamin D3) have been effective . Our patient did not respond to topical therapy, but did respond well to methotrexate. Her dose of methotrexate was titrated according to the severity of her pain. Whereas the exact mechanism by which methotrexate acts in morphea is unknown , a few studies have suggested its efficacy in producing visible improvement of morphea lesions in both adults and children [7, 8, 9]. The treatment protocol for these studies called for a methotrexate dose of 15 mg per week. Our patient responded to a lower dose of 10 to 12.5 mg per week. Importantly, we found that the dose titrated according to severity of pain was effective in improving the patient’s quality of life, as well as improving the clinical appearance of the lesion.
A patient with morphea presenting with pain, as described in this report, is unusual because pain is not a feature typically associated with morphea. Possible explanations for pain in patients with morphea could be conjectured by considering the condition’s pathogenesis. For example, it is possible that the same process involved in autoimmune dysregulation or abnormal cytokine production resulting in morphea also inflames nearby nerves, resulting in pain associated with morphea. “There is a dearth of knowledge about psychosocial functioning among adult patients with morphea,” including pain and its consequential effect on the patients’ well-being . Kroft and colleagues studied psychological well-being in patients with morphea or eosinophilic fasciitis via questionnaires and reported that 32 percent of the 74 patients surveyed experienced pain, 55 percent experienced fatigue, and 22 percent experienced itch . To our knowledge, there are no other documented reports on the percentage of morphea patients presenting with pain or documenting pain by anatomic site.
It has been reported that physical symptoms of pain, itch, and fatigue are severe and chronic stressors in patients with skin diseases . In patients with morphea, such symptoms may be overlooked by their physicians because morphea is generally thought to be asymptomatic. Moreover, in this case presentation the physical examination findings did not correlate with symptoms. The appearance of the lesion responded promptly to systemic steroids, but the patient’s symptoms required several months of methotrexate therapy for pain control. Although our patient was otherwise healthy, pain associated with her morphea lesion was so severe that it interfered with her quality of life, including working. More studies are needed to understand pain associated with morphea. We encourage physicians to assess for such symptoms and to treat aggressively in order to avoid significant morbidity.
While not typical, patients with morphea can experience debilitating pain. We find that titrating methotrexate dose according to the severity of pain helped alleviate pain in a morphea patient who had been previously unresponsive to topical therapy. The unusual but consequential presentation of pain with morphea in this patient underscores the need for physicians to identify pain as an associated symptom in patients with morphea and to provide prompt treatment.
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