Hairless plaque on a woman’s forearm

Morphea is a rare cutaneous inflammatory disease characterized by asymmetric sclerotic plaques.1 It progresses to scar-like sclerosis of the skin, primarily the dermis and subcutaneous fat, and sometimes extends to underlying muscle and bone. It can present in childhood or...

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Morphea is a rare cutaneous inflammatory disease characterized by asymmetric sclerotic plaques.¹ It progresses to scar-like sclerosis of the skin, primarily the dermis and subcutaneous fat, and sometimes extends to underlying muscle and bone. It can present in childhood or later in life and is more common in women than in men. The pathogenesis of morphea involves autoimmune mechanisms, and it is clinically distinct from scleroderma.² Different subtypes of morphea include plaque-type morphea (also known as localized scleroderma), linear morphea, and generalized morphea.¹ 

Morphea was first described in detail by Thomas Addison in 1854; he called it “Alibert’s keloid syndrome.” In 1930, O’Leary and Nomland distinguished morphea from scleroderma.¹ There is still a demand for more research regarding the pathogenesis, classification, and treatment of morphea. 

Information about the epidemiology of morphea is also scarce. A study conducted at the Mayo Clinic identified and followed 82 cases of morphea in Olmsted County between 1960 and 1993. The study concluded that the incidence was 2.7 per 100,000 and increasing by approximately 3.6% per year. The prevalence of morphea at 80 years of age was estimated at 0.2%. The highest prevalence is in Caucasian women.³ 

The average age of adult presentation is mid-40s, and most cases are plaque-type. In children, 90% of cases present between ages 2 and 14 years, with linear morphea being the most common variant.² Half of patients with morphea exhibit disease resolution in 3.8 years. Plaque-type morphea yields the briefest active disease duration; the deep and linear types have longer durations with more frequent systemic involvements, including arthralgia and uveitis. Patients with morphea have a normal life expectancy, further distinguishing it from scleroderma. However, there is greater morbidity associated with the linear type.³ 

Morphea is an inflammatory process leading to imbalanced production and destruction of collagen. The pathogenesis is complex and uncertain. The most widely accepted theory is that the development of morphea is multifactorial, requiring inherent autoimmunity and an environmental trigger. The disease might also be associated with an embryologic origin such as genetic mosaicism or microchimerism.^2,4

The initiating event, likely a local trigger in the skin, causes vascular injury. The vascular injury may be secondary to hypoxia, trauma, infection (Borrelia burgdorferi and CMV have been implicated), oxidative stress, or anti-endothelial cell autoantibodies.⁵ Researchers believe that after the triggering event, morphea follows a pathway similar to that of scleroderma. The damaged vessels release pro-inflammatory signals that recruit lymphocytes. Recruited T-cells secrete pro-fibrotic cytokines, including IL-4, IL-6, and TGF-beta; the latter increases collagen production and decreases protease production. This process causes skin fibrosis.² 

The diagnosis of morphea is based on clinical presentation, which varies with type. Plaque-type morphea first presents in the active inflammatory stage with edematous, erythematous, or dusky violaceous plaques, usually on the trunk. As the lesions mature, they appear as violaceous rings with a white sclerotic center. The plaques usually have a diameter between 2 and 15 cm. Most often, there are multiple asymmetric plaques, but cases with one single lesion also exist. Individual lesions may stay the same size or grow in diameter over time. Disappearance of the violaceous ring marks the resolution of the active stage; at this point the sclerotic plaques become hyperpigmented, anhidrotic, and hairless.¹ 

Linear morphea (the most common type in children) first appears as plaque-type morphea, but then extends in a linear fashion, eventually becoming scar-like. This type of morphea tends to be more severe and has higher morbidity than plaque type. The sclerosis may involve underlying fascia, muscles, tendons, and even bone. When linear morphea extends across a joint, it can result in immobilization. Linear morphea of the forehead and scalp is known as the en coup de sabre type. This type often involves deeper structures and, rarely, can extend to the meninges and brain-causing seizures, focal neurologic deficits, and headaches.⁶ Parry-Romberg syndrome, a severe form of linear morphea, leads to facial atrophy along the trigeminal nerve distribution. Unlike the plaque-type, linear morphea usually does not regress.¹

Generalized morphea is defined as 4 or more morphea plaques involving more than one body site. This category also includes plaque-type morphea that expands rapidly and occupies the trunk in such a way as to limit chest expansion, causing progressive dyspnea. Generalized morphea has the highest rate of extracutaneous manifestations, including arthralgia and fatigue. Other variants of morphea include nodular, bullous, guttate, and atrophoderma of Pasini and Pierini.¹ 

In the early stages of morphea, histology shows a perivascular infiltrate of lymphocytes with few plasma cells and eosinophils in the reticular dermis. Hyalinization and thickening of collagen bundles may also be observed. In later stages, the lymphocytic infiltrate vanishes and the hyalinized collagen bundles appear very crowded. Capillaries wane in number, eccrine glands and hair follicles become atrophic, and collagen expands into the subcutaneous tissues.^1,2 

Patients with morphea often have serum autoantibodies, including antinuclear antibody, anti-ssDNA, antihistone, anti-topoisomerase II, and antiphospholipid antibody. Cytokines that activate lymphocytes, specifically IL-2, IL-4, and IL-6, may also be significantly elevated. Autoantibodies and elevated cytokines are more strongly associated with linear and generalized morphea than plaque-type morphea.⁷ 

Scleroderma (systemic sclerosis) is the number one item on the differential diagnosis for morphea. The two can often be distinguished clinically by the absence in morphea of Raynaud’s phenomenon, nail fold capillary changes, sclerodactyly, and internal organ involvement. Morpheaform plaques must also be differentiated from lichen sclerosus, injection-site sclerosis (from vitamin K, B12, or steroid injections), lipodermatosclerosis, porphyria, eosinophilic fasciitis, chronic graft-versus-host disease, sclerosing congenital melanocytic nevus, or reactions from systemic medications (bleomycin, taxanes, valproic acid, and penicillamine). Morphea can be distinguished based on the clinical picture and histology.¹ 

The treatment plan for morphea depends on the specific type and severity. Current therapies include topical medication, systemic immunosuppressive therapy, and phototherapy. Therapeutics are more effective during the active stage of morphea. 

In cases of uncomplicated plaque-type morphea, topical corticosteroids or topical tacrolimus may be prescribed, although most important is close observation and monitoring of the plaques.⁸ Phototherapy (PUVA and UVA1) can also be used as a treatment for morphea. The radiation increases collagenase expression and reduces inflammation in the dermis. The long-term efficacy of phototherapy has not been demonstrated, but some studies showed regression and softening of morphea plaques.⁹ 

In severe cases of morphea (such as linear morphea), or cases that do not respond to topical therapy, systemic therapies may be used. Methotrexate is a mainstay of treatment, usually combined with systemic corticosteroids; multiple retrospective studies have demonstrated their efficacy in treating morphea. In cases of linear morphea with associated debilitation or deformity, physical therapy and plastic surgery may also be considered.¹⁰ 

The patient in this vignette was diagnosed with plaque type morphea. She was prescribed a potent topical corticosteroid (clobetasol 0.05% ointment) to use twice a day. After several months of use, she noted the lesion had become lighter (closer to her normal skin tone) and much softer. She plans to continue using the topical steroid. 

Talia Jayne Noorily is a medical student at the Baylor College of Medicine, David Rizk is a medical student at the University of South Alabama, and Connie Wang, MD, is a dermatology resident at the Baylor College of Medicine in Houston.

References

1. Rocken M, Ghoreschi K. Morphea and lichen sclerosus. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2012:657-670. 
2. Fett N, Werth VP. Update on morphea: Part I. Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dematol. 2011;64:217-228. 
3. Peterson LS, Nelson AM, Sue WP, et al. The epidemiology of morphea (localized scleroderma) in Olmsted County 1960-1993. J Rheumatol. 1997;24:73-80.
4. Saracino AM, Denton CP, Orteu CH. The molecular pathogenesis of morphoea: from genetics to future treatment targets. Br J Dermatol. 2017;177:34-46. 
5. Sartori-Valinotti JC, Tollefson MC, Reed AM. Updates on morphea: role of vascular injury and advances in treatment. Autoimmune Dis. 2013:2013;467808.
6. Pinho J et al. Localized scleroderma en coup de sabre in the Neurology Clinic. Mult Scler Relat Disord. 2016;8:96-98.
7. Taehara K, Sato S. Localized scleroderma is an autoimmune disorder. Rheumatol. 2005;44:274-279.
8. Fett N. Morphea: Evidence-based recommendations for treatment. Ind J Dermatol Venereol Leprol. 2012;78:135-141.
9. Hassani J, Feldman SR. Phototherapy in scleroderma. Dermatol Ther Careta MF, Romiti R. Localized scleroderma: clinical spectrum and therapeutic update. An Bras Dermatol. 2015;90:62-73.