What is Cutis laxa, who gets it and how is it treated?

Cutis Laxa: Who Gets It and How to Treat

What is Cutis Laxa?

Cutis laxa is a rare connective tissue disorder characterized by loose, wrinkled, sagging, and inelastic skin that lacks normal elasticity, making affected individuals appear prematurely aged. 1

The condition results from abnormal synthesis or destruction of elastic fibers in the skin and other organs, leading to redundant, hanging skin folds particularly on the face and trunk. 1, 2

Who Gets Cutis Laxa?

Inherited Forms

Inherited cutis laxa occurs due to genetic defects affecting extracellular matrix proteins and can follow three inheritance patterns:

• Autosomal dominant inheritance - typically milder with primarily skin involvement 1
• Autosomal recessive inheritance - more severe with multisystem involvement 1
• X-linked recessive inheritance - associated with Occipital Horn Syndrome, featuring connective tissue abnormalities including hernias, joint laxity, and bladder diverticula 3

Inherited forms often present in infancy or childhood and are associated with inborn errors of metabolism in some cases. 1 These patients typically have multisystem involvement affecting cardiovascular, pulmonary, and gastrointestinal systems, leading to severe and sometimes lethal complications. 1, 2

Acquired Forms

Acquired cutis laxa develops in adults, typically between ages 35-45 years, and is associated with:

• Inflammatory cutaneous eruptions - particularly urticarial vasculitis and other inflammatory dermatoses 4, 5
• Autoimmune diseases - including rheumatoid arthritis and systemic lupus erythematosus 4, 5
• Plasma cell dyscrasias - monoclonal gammopathies, smoldering multiple myeloma 5
• Medications - various drug exposures 4, 1
• Infections 1
• Neoplasms 4

The acquired form typically shows cephalocaudal (head-to-toe) progression and may occur with or without a preceding inflammatory eruption. 4, 5

Pathophysiology of Acquired Forms

The destruction of elastic fibers in acquired cutis laxa appears related to infiltration of inflammatory cells in the dermis, with chemical mediators playing a major role in elastin degradation. 4

Clinical Presentation

Skin Manifestations

• Loose, wrinkled, redundant skin with complete loss of elasticity (unlike Ehlers-Danlos syndrome which shows hyperelasticity) 3, 2
• Premature aging appearance - patients appear significantly older than their chronological age 4
• Smooth, sagging folds particularly on mid-torso, face, and trunk 4, 2
• May be localized or generalized 5

Systemic Complications

Inherited cutis laxa frequently involves multiple organ systems:

• Pulmonary complications - emphysema, bronchomalacia leading to respiratory failure 3, 2
• Cardiovascular abnormalities - cardiomyopathy, aortitis, vascular anomalies 6, 5
• Gastrointestinal involvement - hernias, diverticula 3
• Genitourinary problems - bladder diverticula, renal failure 3, 2
• Skeletal findings - joint laxity, occipital horn exostoses in X-linked forms 3
• Neurological features - intellectual disability, white matter abnormalities 6

Diagnostic Workup

Essential Evaluations

Complete clinical and family history is mandatory to distinguish inherited from acquired forms. 4

Skin biopsy with histologic analysis showing:

• Decreased or absent elastic fibers 4
• Inflammatory cell infiltration in dermis (acquired forms) 4
• Elastolysis on histopathology 2, 5

Systemic Evaluation for Acquired Forms

When acquired cutis laxa is diagnosed, comprehensive systemic workup must include:

• Serum protein electrophoresis to detect monoclonal gammopathy 5
• Complete blood count to evaluate for anemia and plasma cell disorders 5
• Autoimmune serologies including ANA, RF for underlying rheumatologic disease 5
• Cardiovascular imaging to assess for aortitis or cardiomyopathy 6, 5
• Pulmonary function tests to detect emphysema or restrictive lung disease 2
• Renal function assessment 2

Genetic Testing

Mutation analysis of known cutis laxa genes (EFEMP2, ELN, FBLN5, LTBP4, ATP7A) should be performed in suspected inherited cases, though some novel phenotypes may test negative. 6

Treatment Approach

Critical Reality

To date, no effective treatment is available that reverses or halts the progression of cutis laxa itself. 1

Management Strategy

Treatment is entirely supportive and focuses on managing complications rather than the underlying elastin defect:

For Acquired Forms with Inflammatory Component

• Antihistamines may relieve pruritus associated with urticarial eruptions, but do not improve the cutis laxa or hyperpigmentation 4
• High-dose corticosteroids (prednisone) for associated vasculitis 5
• Immunosuppressive therapy (cyclophosphamide, bortezomib, dexamethasone) for underlying plasma cell dyscrasias 5

Important caveat: Even successful treatment of underlying conditions (myeloma, vasculitis) does not improve the established cutis laxa. 5

Systemic Complication Management

• Pulmonary support for emphysema and respiratory failure 2
• Cardiovascular monitoring and treatment for cardiomyopathy and vascular abnormalities 6, 5
• Surgical intervention for hernias, diverticula, and skeletal complications 3
• Renal replacement therapy if end-stage renal disease develops 2

Cosmetic Considerations

Surgical skin excision may be considered for severe cosmetic disfigurement, but this addresses appearance only and does not treat the underlying disorder. 1

Prognosis

Inherited forms with multisystem involvement carry significant morbidity and mortality:

• Death from respiratory failure typically occurs in the fourth to fifth decade 2
• Cardiovascular complications contribute to early mortality 6
• Some forms are lethal in infancy or childhood 1

Acquired forms have variable prognosis depending on underlying etiology and systemic involvement. 5

Key Clinical Pitfalls

Do not confuse cutis laxa with Ehlers-Danlos syndrome - cutis laxa shows complete lack of elasticity while Ehlers-Danlos shows hyperelasticity. 3, 2

Always evaluate for underlying systemic disease in acquired cases - particularly monoclonal gammopathy, autoimmune disease, and malignancy, as these require specific treatment. 5

Recognize that skin improvement with treatment of underlying conditions is unlikely - set realistic expectations with patients that established cutis laxa persists despite treating associated diseases. 5

Monitor for life-threatening complications - particularly respiratory failure from emphysema and cardiovascular events, which are the primary causes of mortality. 2, 5