Understanding Morphea: A Rare Autoimmune Condition Affecting the Skin

Imagine waking up one morning to find unusual patches on your skin, which gradually harden and thicken over time. This is the reality for individuals living with morphea, a rare autoimmune condition also known as localized scleroderma. Characterized by inflammation and excessive collagen deposition, morphea leads to hardened skin and underlying tissue damage.

The condition can affect anyone, but it is more prevalent among Caucasian women. According to the Mayo Clinic, the exact cause of morphea remains unknown, but it is believed to be linked to an abnormal immune response. As the condition progresses, it can lead to significant changes in the skin’s appearance and texture.

Key Takeaways

• Morphea is a rare autoimmune condition that causes inflammation and hardening of the skin.
• It is more common among Caucasian women, with a female-to-male ratio of approximately 3:1.
• The condition can lead to significant changes in the skin’s appearance and texture.
• Understanding the causes and symptoms of morphea is crucial for proper diagnosis and treatment.
• Morphea can have a significant impact on a person’s quality of life.

What Is Morphea (Localized Scleroderma)

Morphea is a form of scleroderma that is confined to the skin and sometimes the underlying tissues, without the internal organ involvement seen in systemic sclerosis. This distinction is crucial for understanding the condition’s clinical features and implications.

Definition and Clinical Features

Morphea, or localized scleroderma, is characterized by the deposition of collagen in the skin, leading to thickening and hardening of the affected areas. The condition can manifest in various forms, including plaque morphea, linear scleroderma, and generalized morphea, each with distinct clinical features. The primary clinical feature of morphea is the presence of one or more lesions on the skin, which can vary in size, shape, and color.

The lesions associated with morphea can be accompanied by other symptoms such as inflammation, itching, and pain. In some cases, morphea can affect underlying tissues, including subcutaneous fat, fascia, and occasionally muscle and bone. The condition’s impact on the skin and underlying tissues can lead to significant morbidity, including cosmetic disfigurement and functional impairment.

Morphea vs. Systemic Sclerosis

A key aspect of understanding morphea is distinguishing it from systemic sclerosis. The primary distinction between the two conditions lies in the pattern and extent of tissue involvement. While morphea is limited to the skin and sometimes underlying tissues, systemic sclerosis involves internal organs such as the lungs, heart, kidneys, and gastrointestinal tract.

• Morphea primarily affects the skin, whereas systemic sclerosis has a broader range of organ involvement.
• Patients with morphea typically do not experience Raynaud’s phenomenon, a hallmark symptom of systemic sclerosis.
• Laboratory findings differ between the two conditions, with systemic sclerosis often showing specific autoantibody patterns not typically seen in morphea.
• Despite these distinctions, recent research suggests that some patients with morphea may experience mild systemic symptoms or have subclinical internal organ involvement.

The prognosis for morphea is generally more favorable than for systemic sclerosis, though both conditions can cause significant morbidity. Understanding the differences between morphea and systemic sclerosis is essential for accurate diagnosis and appropriate management.

Epidemiology and Demographics

Understanding the epidemiology and demographics of morphea is crucial for early diagnosis and treatment. Morphea, or localized scleroderma, is a condition that affects various populations differently.

Prevalence and Incidence Rates

Morphea’s prevalence varies across different age groups and populations. It is estimated that about 50 out of every 100,000 children are affected by this condition. The condition is more common in Caucasians, and most patients are female.

The prevalence of morphea in different populations can be summarized as follows:

Age and Gender Distribution

Morphea demonstrates a clear gender predilection, affecting women approximately three times more frequently than men across most subtypes. The condition exhibits a bimodal age distribution, with peak incidence occurring in children between ages 6-10 years and again in the fifth decade of life (40-50 years).

In pediatric populations, morphea is the most common form of scleroderma. Certain subtypes of morphea show distinct demographic patterns; for example, linear scleroderma is more common in children and adolescents, while plaque morphea is more frequently diagnosed in adults.

Overall, understanding these epidemiological and demographic patterns is essential for managing morphea effectively in various patients.

Classification of Morphea

The classification of morphea is crucial for understanding its diverse manifestations and guiding treatment. Morphea, also known as localized scleroderma, encompasses a range of clinical subtypes characterized by varying degrees of skin and tissue involvement.

Plaque Morphea

Plaque morphea is the most common subtype, characterized by one or more oval or round patches on the skin, often with a violaceous border and central sclerosis. These lesions can be found on various parts of the body and may be accompanied by inflammation and induration.

Linear Scleroderma

Linear scleroderma presents as a linear band or streak of sclerotic skin, often affecting the limbs or face. This subtype can lead to significant cosmetic and functional impairment, particularly if it involves joints or growth plates in children.

Generalized Morphea

Generalized morphea involves multiple lesions or widespread skin involvement, often with significant morbidity. This subtype can be disabling due to the extent of skin and potential underlying tissue involvement.

Deep Morphea

Deep morphea, also known as morphea profunda, involves deeper tissue layers, including fascia and muscle. It can present with significant induration and may be associated with disability due to the depth of tissue involvement.

Bullous Morphea

Bullous morphea is a rare form of morphea characterized by the development of fluid-filled blisters or erosions on existing morphea lesions. The bullae typically develop within or adjacent to sclerotic plaques and contain clear or hemorrhagic fluid. Histologically, bullous morphea shows subepidermal blistering in addition to the typical dermal sclerosis seen in other forms of morphea. Accurate diagnosis requires histopathological examination to distinguish it from other bullous diseases. Treatment approaches generally follow those for other morphea subtypes, with additional attention to wound care for eroded areas.

Linear Scleroderma of the Face

Facial manifestations of linear scleroderma can be particularly distressing due to their visible nature and potential for long-term disfigurement. The condition can affect various aspects of a person’s life, from their self-esteem to their overall well-being. Two significant forms of linear scleroderma that affect the face are “En Coup de Sabre” and Progressive Facial Hemiatrophy (Parry-Romberg Syndrome).

“En Coup de Sabre”

“En Coup de Sabre” is a form of linear scleroderma that typically affects the frontoparietal region of the face. It is characterized by a linear or band-like pattern of sclerosis, often accompanied by changes in skin pigmentation and potentially leading to significant facial asymmetry. The condition can be associated with neurological symptoms, including seizures and headaches, in some cases.

The exact cause of “En Coup de Sabre” remains unknown, but it is believed to involve a combination of genetic predisposition and environmental triggers. Treatment options vary depending on the severity and progression of the condition, ranging from topical therapies to systemic medications aimed at halting disease progression.

Progressive Facial Hemiatrophy (Parry-Romberg Syndrome)

Progressive Facial Hemiatrophy (PFH), also known as Parry-Romberg Syndrome, is a rare disorder characterized by progressive unilateral atrophy of facial tissues. Unlike linear scleroderma “en coup de sabre,” PFH primarily affects the subcutaneous tissues, muscles, and bones with minimal or absent skin sclerosis. The condition typically develops during the first or second decade of life and progresses slowly over a period of 2 to 20 years before becoming stationary.

PFH causes atrophy of the skin, subcutaneous tissue, muscle, and underlying bony structures on one side of the face, most commonly affecting areas innervated by the trigeminal nerve. The area below the eye is most frequently involved, creating a sunken appearance on the affected side of the face. Some patients experience prodromal symptoms such as facial pain or discoloration before the onset of visible atrophy.

Neurological complications occur in about 20% of PFH cases, and ophthalmic complications in approximately 15% of cases. The coexistence of PFH and linear scleroderma “en coup de sabre” in approximately 20-37% of patients has led some experts to consider them part of the same disease spectrum.

Etiology and Pathogenesis

Morphea’s etiology is multifactorial, involving a complex interplay of autoimmune, genetic, and environmental elements. Understanding these factors is crucial for comprehending the disease’s progression and developing effective treatments.

Autoimmune Factors

Autoimmune factors are believed to play a significant role in the development of morphea. The presence of high-titer antinuclear antibodies in some patients suggests an autoimmune component. This is further supported by the association of morphea with other autoimmune diseases, indicating a potential shared underlying mechanism.

Genetic Predisposition

Genetic predisposition is another critical aspect of morphea’s etiology. Certain genetic factors may make individuals more susceptible to developing the condition when exposed to specific triggers. Research into the genetic underpinnings of morphea is ongoing, with studies aiming to identify specific genes or gene expressions that contribute to the disease.

Environmental Triggers

Various environmental factors have been implicated as potential triggers for morphea in genetically susceptible individuals. Infection with Borrelia burgdorferi, the causative agent of Lyme disease, has been associated with a subset of morphea cases, particularly in European populations. This has led to the identification of “Borrelia-associated early onset morphea,” characterized by disease onset at a younger age and evident autoimmune phenomena.

Other environmental triggers include physical trauma, radiation therapy, and certain medications such as bleomycin and TNF-alpha inhibitors. The “two-hit hypothesis” suggests that both genetic predisposition and environmental triggers are necessary for morphea development.

The interplay between these factors contributes to the complexity of morphea’s etiology and pathogenesis. Further research is needed to fully understand the mechanisms involved and to develop targeted therapeutic strategies.

Pathophysiology of Skin Changes

Understanding the pathophysiology of morphea is crucial for grasping how this condition affects the skin. Morphea, or localized scleroderma, involves a complex interplay of inflammatory processes and excessive collagen production, leading to significant changes in skin and subcutaneous tissue.

Inflammation Process

The inflammation process in morphea is a critical initial step that triggers subsequent tissue changes. Inflammatory cells and cytokines play a pivotal role in activating fibroblasts, which then produce excessive amounts of collagen. This process disrupts the normal architecture of the dermis, leading to the characteristic hardening and thickening of the skin associated with morphea.

Collagen Overproduction and Fibrosis

The hallmark of morphea pathophysiology is the overproduction and deposition of collagen, resulting in fibrosis of the affected tissue. Activated fibroblasts and myofibroblasts produce abnormally large amounts of collagen, primarily types I and III, and other extracellular matrix components. This overproduction is stimulated by transforming growth factor-beta (TGF-β), a key profibrotic cytokine upregulated in morphea lesions.

In morphea, the normal basket-weave pattern of the dermis is replaced by dense collagen bundles, extending into the subcutaneous fat and causing the characteristic “bound down” appearance. As fibrosis progresses, it can lead to atrophy of skin appendages and subcutaneous fat, resulting in the depressed appearance of mature lesions.

Clinical Manifestations and Symptoms

Patients with morphea often experience a range of symptoms, from mild skin hardening to severe joint pain and mobility issues. The clinical manifestations of morphea can vary significantly depending on the location, depth, and extent of the lesions.

Early Signs and Inflammatory Phase

In the early stages, morphea typically presents as an inflammatory phase characterized by erythema and edema. This initial inflammation can be accompanied by mild discomfort or pain. As the condition progresses, the affected skin begins to thicken and harden.

Skin Hardening and Atrophy

Skin hardening in morphea is a result of excessive collagen deposition, leading to sclerosis. Over time, the affected skin may also undergo atrophy, becoming thinner and more fragile. This progression can result in significant disfigurement and discomfort for patients.

Pain and Functional Limitations

The extent of pain and functional limitations in morphea varies significantly among patients. Approximately 40% of patients report pain or discomfort, ranging from mild tenderness to significant neuropathic pain. When morphea affects joints or underlying tissues, it can lead to contractures and mobility restrictions, further complicating the clinical picture.

In conclusion, morphea presents with a wide range of clinical manifestations and symptoms, significantly impacting the quality of life for those affected. Understanding these symptoms is crucial for effective management and treatment of the condition.

Extracutaneous Manifestations

While morphea is known for its cutaneous manifestations, extracutaneous involvement is increasingly recognized. This aspect of the disease is particularly significant in generalized and linear subtypes of morphea.

Musculoskeletal Involvement

Musculoskeletal involvement is a common extracutaneous manifestation in patients with morphea. This can include arthritis and other joint-related issues, significantly impacting the quality of life for these patients. In some cases, musculoskeletal involvement can lead to significant disability.

Neurological Complications

Neurological complications are also observed in morphea patients, particularly those with linear scleroderma of the face or head. These complications can range from seizures to headaches and other neurological symptoms. The exact mechanism behind these neurological involvement is not fully understood but is thought to be related to the inflammatory nature of the disease.

Other Organ System Involvement

A variety of other organ systems can be involved in morphea, including the eyes, gastrointestinal tract, and respiratory system. Ocular involvement can lead to conditions such as uveitis and episcleritis. Gastrointestinal manifestations include gastroesophageal reflux disease (GERD) and esophagitis. Pulmonary involvement, though rare, can result in restrictive lung disease.

The diverse range of extracutaneous manifestations in morphea highlights the complexity of the disease and the need for comprehensive management strategies that address both cutaneous and extracutaneous aspects.

Morphea in Children

Pediatric morphea, particularly linear scleroderma, can have significant implications on a child’s growth and development. The condition manifests differently in children compared to adults, often leading to unique challenges in diagnosis and treatment.

Unique Presentation in Pediatric Patients

In children, morphea can present with distinct characteristics that differentiate it from the adult form. Linear scleroderma is a common subtype in pediatric patients, often affecting the limbs or face. This subtype can lead to significant morbidity due to its potential to cause growth disturbances and deformities.

Key Features:

• Linear scleroderma affecting the limbs or face
• Potential for growth disturbances and deformities
• Higher risk of musculoskeletal involvement

Growth and Development Concerns

Growth and development concerns represent a significant challenge in managing pediatric morphea. When linear morphea crosses joints or affects growth plates, it can cause limb length discrepancies, joint contractures, and muscle atrophy. Craniofacial linear scleroderma can lead to facial asymmetry and jaw growth abnormalities, further complicating the clinical picture.

The impact on growth and development can be profound, necessitating a multidisciplinary approach to care. Early aggressive treatment is crucial to prevent irreversible growth abnormalities. The therapeutic window is narrower in children, making timely intervention essential.

Growth and Development Implications:

• Limb length discrepancies and joint contractures
• Facial asymmetry and jaw growth abnormalities
• Psychological impact on body image and quality of life

A multidisciplinary care team involving rheumatologists, dermatologists, orthopedic surgeons, physical therapists, and psychologists is essential for addressing these complex issues.

Diagnostic Approach

Morphea diagnosis requires a thorough diagnostic approach, encompassing clinical evaluation, skin biopsy findings, and laboratory assessments. This multifaceted strategy is essential for accurately diagnosing morphea and differentiating it from other conditions.

Clinical Evaluation

A comprehensive clinical evaluation is the first step in diagnosing morphea. This involves a detailed medical history and physical examination to identify characteristic skin lesions and assess their distribution and severity. Clinicians should be aware of the various clinical forms of morphea, including plaque, linear, generalized, deep, and bullous types, as each has distinct features.

Clinical evaluation is crucial for identifying the early signs of morphea, such as erythema and edema, which precede the development of sclerosis. The presence of lesions in various stages of development can provide important diagnostic clues.

Skin Biopsy Findings

Skin biopsy is a valuable diagnostic tool in morphea, providing histopathological evidence that can support the clinical diagnosis. Biopsy specimens typically show increased collagen deposition and a characteristic inflammatory infiltrate, which may include lymphocytes and plasma cells.

The histological features can vary depending on the stage of the disease. In early morphea, biopsies often reveal perivascular and interstitial lymphocytic infiltrates, while in later stages, there is dermal thickening with collagen bundles arranged in a parallel fashion to the epidermis.

Laboratory and Immunological Tests

Laboratory tests play a supportive role in the diagnosis of morphea, primarily used to exclude other diagnoses and assess for potential systemic involvement. Various autoantibodies have been associated with morphea, including antinuclear antibodies (ANA), anti-histone antibodies, and anti-topoisomerase IIa antibodies.

In patients with morphea, these tests can provide valuable information, although their utility in predicting disease course or severity is limited. For instance, approximately 50% of patients have positive ANA, and certain autoantibodies are more frequently found in specific subtypes of morphea. In some cases, additional tests may be necessary to rule out other conditions or assess systemic involvement.

Imaging Studies and Assessment

Imaging studies play a crucial role in the diagnosis and assessment of morphea, enabling healthcare providers to determine the best course of treatment. These studies help evaluate the extent and severity of the disease, guiding therapeutic decisions.

The use of advanced imaging techniques has become increasingly important in managing morphea. Two key imaging modalities used are MRI and CT scans.

MRI and CT Scans

MRI (Magnetic Resonance Imaging) and CT (Computed Tomography) scans are valuable tools in assessing morphea. MRI is particularly useful for evaluating the extent of skin and soft tissue involvement, as well as detecting any potential musculoskeletal or neurological complications. CT scans, on the other hand, provide detailed images of internal structures and can help identify any potential organ involvement.

Other Diagnostic Techniques

Beyond conventional imaging, several specialized diagnostic techniques have emerged to aid in the assessment and monitoring of morphea. These include:

• Ultrasound with color Doppler to evaluate skin thickness and blood flow in morphea lesions.
• Infrared thermography to detect temperature differences between active inflammatory lesions and surrounding normal skin.
• Laser Doppler flowmetry to measure microcirculation in the skin and identify increased blood flow in early, active morphea lesions.
• Durometry to provide objective measurement of skin hardness and monitor disease progression.
• Computerized skin scoring methods using digital photography and image analysis software to assess lesion size and pigmentation changes.
• Optical coherence tomography to offer high-resolution imaging of skin microstructure and detect subtle changes in collagen organization.

These advanced techniques enhance the ability to diagnose and manage morphea effectively, allowing for more personalized treatment plans and improved patient outcomes.

Treatment Options for Morphea

The management of morphea involves a multifaceted approach, incorporating various treatment modalities to address the diverse manifestations of the disease. The choice of therapy depends on the extent and severity of skin involvement, as well as the presence of extracutaneous symptoms.

Topical Therapies

Topical treatments are often considered for patients with limited skin involvement. These may include corticosteroids, which can help reduce inflammation, and topical immunomodulators, such as tacrolimus, which can be effective in managing localized lesions.

Systemic Medications

For more extensive or severe cases of morphea, systemic medications may be necessary. These can include corticosteroids, methotrexate, and other immunosuppressive agents, which aim to reduce inflammation and prevent disease progression. The choice of systemic therapy is typically guided by the severity of symptoms and the presence of extracutaneous involvement.

Phototherapy Approaches

Phototherapy represents an effective treatment option for morphea, particularly for patients with extensive cutaneous involvement or contraindications to systemic immunosuppressive therapy. UVA1 phototherapy, with its ability to penetrate into the deeper dermis and subcutaneous tissue, is the most extensively studied light therapy for morphea. The mechanism of action of UVA1 includes induction of collagenase expression, apoptosis of skin-infiltrating T cells, and decreased production of proinflammatory cytokines.

UVA1 phototherapy is typically administered at a medium dose (50-70 J/cm²), 3-5 times weekly for 20-30 sessions. While the optimal dosing regimen remains undefined, this approach has shown efficacy in managing morphea. Narrowband UVB phototherapy has also demonstrated effectiveness, particularly for superficial lesions, and may be more widely available than UVA1. PUVA therapy, either as bath PUVA or oral PUVA, represents another phototherapy option with demonstrated efficacy in morphea.

Despite the benefits of phototherapy, limitations include limited availability, time commitment for treatments, potential phototoxicity, and theoretical concerns about long-term photocarcinogenesis. However, for many patients, the benefits of phototherapy in managing morphea outweigh these limitations.

Advanced and Emerging Treatments

The treatment landscape for Morphea is rapidly evolving with the introduction of advanced and emerging therapies. As our understanding of the disease’s pathophysiology deepens, novel therapeutic approaches are being developed to target specific pathways involved in Morphea.

Immunosuppressive Therapies

For patients with severe or refractory Morphea, immunosuppressive therapies have shown promise. Methotrexate remains a cornerstone in the treatment of Morphea, often used in combination with corticosteroids. Other immunosuppressive agents, including mycophenolate mofetil, are also utilized to control disease activity.

A significant advancement in immunosuppressive therapy is the use of biologic agents. TNF inhibitors, such as infliximab and adalimumab, have been effective in managing Morphea in some cases. Other biologics, including abatacept and rituximab, are being explored for their potential in treating this condition.

Biologic Agents and Novel Approaches

Beyond traditional immunosuppression, several novel approaches are being investigated for the treatment of Morphea. Janus kinase (JAK) inhibitors, such as tofacitinib and baricitinib, represent a promising new class of medications. These drugs block multiple cytokine pathways involved in inflammation and fibrosis, offering a targeted approach to managing Morphea.

Other emerging therapies include antifibrotic agents like pirfenidone and nintedanib, originally developed for idiopathic pulmonary fibrosis. These medications have shown potential in inhibiting fibroblast proliferation and collagen production, key factors in the pathogenesis of Morphea.

The development of therapies targeting specific profibrotic cytokines, such as anti-TGF-β antibodies, is also underway. Additionally, stem cell therapies, particularly mesenchymal stem cells with their immunomodulatory and antifibrotic properties, are under investigation for severe, refractory Morphea.

Supportive Care and Rehabilitation

The impact of morphea on patients extends beyond the physical symptoms, necessitating a comprehensive supportive care and rehabilitation strategy. This approach is crucial for addressing the multifaceted challenges posed by the condition, improving overall quality of life.

Physical and Occupational Therapy

Physical and occupational therapy are vital components of supportive care for morphea patients. These therapies help maintain flexibility, strength, and functional ability, particularly in cases where the condition affects the musculoskeletal system. According to a study published in the National Center for Biotechnology Information, a multidisciplinary approach including physical therapy can significantly improve outcomes for patients with morphea.

Physical therapy focuses on exercises and interventions to improve mobility and reduce stiffness, while occupational therapy helps patients adapt to their condition and perform daily activities more effectively. Both therapies are tailored to the individual’s specific needs and the extent of their condition.

Cosmetic Interventions

Cosmetic interventions play a significant role in addressing the visible aspects of morphea lesions, which can have a profound impact on patients’ psychological well-being and quality of life. Techniques such as camouflage makeup using specialized medical cosmetic products can effectively conceal hyperpigmented or hypopigmented lesions on visible areas like the face and hands.

Other cosmetic approaches include dermal fillers to correct facial volume loss and contour defects, particularly in cases of craniofacial morphea or Parry-Romberg syndrome. Autologous fat grafting offers a more permanent solution for facial volume restoration. Laser therapy, including fractional ablative lasers and vascular lasers, can improve the appearance of atrophic scars and persistent erythema in mature morphea lesions.

As noted by experts, the timing of cosmetic interventions is crucial, with most procedures best performed after the disease has been inactive for at least 1-2 years to minimize the risk of recurrence or progression. This comprehensive approach to supportive care and rehabilitation underscores the importance of addressing both the physical and aesthetic aspects of morphea to improve patients’ overall well-being.

Living with Morphea: Practical Considerations

For individuals living with morphea, navigating the complexities of the disease is crucial for maintaining a good quality of life. Morphea, a chronic condition characterized by localized scleroderma, can have a profound impact on both physical health and psychological well-being.

Daily Management Strategies

Effective management of morphea involves regular monitoring and proactive measures. Regular eye and skin exams are essential for spotting serious complications that may require treatment. Localized scleroderma can persist for years or recur after years of inactive disease, making ongoing vigilance crucial.

Patients can benefit from adopting daily routines that help manage symptoms. This may include gentle skin care practices, protective measures against injury, and exercises to maintain flexibility and range of motion. By taking these steps, individuals with morphea can reduce the risk of complications and improve their overall quality of life.

Psychosocial Impact and Support Resources

The psychosocial impact of morphea should not be underestimated. The condition can affect body image, self-esteem, and quality of life, particularly when lesions are visible or cause functional limitations. Studies have shown that depression and anxiety are common among morphea patients, with prevalence rates ranging from 20-40%.

Support groups, both in-person and online, offer valuable emotional support, practical advice, and a sense of community for patients and their families. Organizations such as the Scleroderma Foundation and the Morphea Research Registry provide educational resources, support networks, and information about clinical trials. Multidisciplinary care teams, including mental health professionals, can address the psychological aspects of living with morphea, ensuring comprehensive care.

Prognosis and Long-Term Outlook

The prognosis for individuals with morphea is complex and varies significantly based on several factors.

The subtype of morphea, extent of disease involvement, and age at onset are crucial in determining the long-term outlook. Plaque morphea typically follows a self-limited course, with active disease lasting 3-5 years, followed by gradual softening of lesions. However, residual changes often persist.

In contrast, linear morphea, particularly in children, tends to have a more prolonged course with higher rates of recurrence and progression, requiring longer treatment periods. Approximately 20-30% of patients experience disease reactivation after periods of quiescence.

Early, aggressive treatment appears to improve long-term outcomes, especially in preventing irreversible functional impairment in high-risk subtypes. Additionally, extracutaneous manifestations may persist or develop even after skin lesions become inactive.

Despite its chronic nature, morphea is rarely life-threatening, with most patients maintaining good overall health and normal life expectancy. However, growth-related complications in children with linear morphea may continue to evolve during puberty, necessitating ongoing monitoring.