Cutis Laxa

Cutis Laxa (Latin; = loose skin) The most obvious clinical feature is loose, wrinkled, sagging skin which has reduced or absent elastic recoil. Different sub-types of the condition are associated with serious skeletal, developmental and internal organ complications (cardiovascular, respiratory, GI tract, GU systems, etc.) The underlying pathology behind cutis laxa is almost always due to damage to or loss of the dermal elastic fibres The loose skin may be especially noticeable affecting the face, neck, armpits and groin

Cutis Laxa A extremely rare disorder of connective tissue Affects both genders equally, and has been found in all races There are both inherited and acquired forms – the acquired form is even more rare than the inherited form It is an extremely rare condition, with only up to 200-400 affected families documented in the literature so far The acquired form is even rarer than the inherited/genetic form The skin in different to the stretchy skin seen in Ehlers-Danlos syndrome, and wound healing is normal

Inherited Cutis Laxa Can be caused by mutation in various genes; most of which are involved in the formation or function of elastic fibres There are AD, AR and X-linked types It is thought that the known genetic abnormalities still only account for a small percentage of all cases of cutis laxa Elastic fibres usually act in providing the skin, lungs and blood vessels with elasticity It is likely there are many other genetic mutations that have yet to be identified

Inherited Cutis Laxa (2) Autosomal dominant Associations can include hernias, genital prolapse, and GI diverticulae. Rarely, aortic aneurysms, pulmonary artery stenosis, cardiac valve anomalies, bronchiectasis and emphysema Caused by mutations in the elastin and fibrillin-5 genes (types 1 and 2 respectively) AD type – clinical diversity. Usually less severe than the AR form, and patients can have a normal life-expectancy

Inherited Cutis Laxa (3) X-linked – also known as Occiptal-Horn Syndrome Hyper-elastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. Sometimes mild neurologic impairment, and bony abnormalities of the occiput

Inherited Cutis Laxa (4) Three sub-types of autosomal recessive cutis laxa , each of which has further sub-classifications Type 1 Type 2 Type 3 Lung atelectasis , emphysema, GI and GU diverticulae, vascular anomalies; cranial anomalies, joint laxity, hip dislocation, and inguinal hernias Variable severity of cutis laxa, abnormal growth, bone dystrophy and other skeletal abnormalities, joint laxity and developmental delay Characteristic facial appearance, eye abnormalities including cataracts; hyper-mobile joints, profound developmental delay, seizures, FTT A highly heterogeneous clinical spectrum with regards to organ involvement and severity

Acquired Cutis Laxa Also known as generalized elastolysis Most cases associated with internal organ involvement, including emphysema, aortic aneurysms and GI tract diverticulae. Hernias and patellar tendon ruptures have also been reported In many cases of acquired cutis laxa, skin involvement first affects the face and neck, and progresses in a cephalo-caudal fashion May occur following a severe illness with fever and rash. Up to half of cases are associated with a preceding inflammatory eruption, such as urticaria, eczema, or erythema multiforme

Acquired Cutis Laxa - precipitants Underlying systemic diseases incl. lupus, RA, sarcoidosis, or complement deficiency May be preceded by urticaria, angioedema, or local or generalized inflammatory skin disease. This form is typified by intense, episodic skin inflammation and recurrent erythematous plaques. Systemic manifestations, such as fever, malaise, and ↑WCC, often accompany the inflammation In the post-inflammatory form, the skin laxity that follows is limited to areas of previous inflammation The picture shows a patient reported in a case study who had inflammatory arthritis, where the cutis laxa was limited to distal areas (where the arthritis had been)

Acquired Cutis Laxa - precipitants Drug reactions, e.g. penicillin SE of medications that remove copper from the body. Pts with Wilson’s disease are at particular risk due to the use of penicillamine Wilson’s disease = AR condition in which copper accumulates in the tissues

Acquired Cutis Laxa - precipitants Secondary to infections or cancer treatments Rare manifestation of haematological malignancies, including myeloma, MGUS, and heavy-chain deposition disease Arch Dermatol. 2011 Mar;147(3):323-8. Generalized acquired cutis laxa associated with multiple myeloma with biphenotypic IgG-λ and IgA-κ gammopathy following treatment of a nodal plasmacytoma. New HD, Callen JP. From this paper – 48 year old male, underwent treatment of an axillary lymph node plasmacytoma with surgery and radiation 4 years prior to his cutaneous changes and had been clinically monitored with a diagnosis of MGUS. Cutaneous manifestations prompted a systemic evaluation demonstrating a persistent monoclonal IgG spike on immunofixation electrophoresis and lytic bone lesions. He was later found to have multiple myeloma

Differential Diagnosis Ehlers-Danlos syndrome Pseudoxanthoma elasticum Granulomatous slack skin (variant of cutaneous T-cell lymphoma) Various eponymous syndromes EDS - a heterogeneous group of inherited connective-tissue disorders characterized by joint hypermobility, cutaneous fragility, and hyperextensibility. All involve a genetic defect in collagen and connective-tissue synthesis and structure PXE is a disorder that is characterized by the accumulation of deposits of calcium and other minerals (mineralization) in elastic fibers Left to right – EDS, PXE and CL

Diagnosis and Work-Up Examination, family history, skeletal survey, developmental assessment Correct Dx of hereditary forms is essential for genetic counselling Acquired cases, screen for potential associated conditions – incl. myeloma, auto-immune screen, complement levels, and serum copper studies ECG, CXR, lung function studies, echo, ophthalmology assessment etc. are all required to screen for internal organ involvement

Diagnosis and Work-Up Skin biopsy – with all types typical histology should show on elastic fibre stains a ↓ in the number of elastic fibres throughout the dermis, with remaining fibres being abnormal or fragmented. In severe cases, no fibres may be present, but only fine, dustlike particles scattered throughout the dermis. In cases preceded by an inflammatory eruption, the inflammatory infiltrate may be seen.

Management No specific treatment - management is symptomatic Dapsone may be used in acute acquired cases with associated inflammation After diagnosis, patients should be screened for internal organ involvement and require regular surveillance Skin – surgery may have good cosmetic effect, but the skin laxity can come back

Management Hernias can be corrected surgically, and excess skin can be removed with plastic surgery Beta-blockers may be help prevent growth of aortic aneurysms Environmental triggers such as cigarette smoking (can worsen lung disease), and sun bathing (can damage skin), should be avoided