Are You Confident of the Diagnosis?
Cutis laxa is a heterogeneous group of rare disorders causing laxity of the integument. It can affect the skin in a localized or generalized manner in acquired cutis laxa, whereas skin involvement is typically generalized and paired with variable systemic involvement in the heritable forms. The prevalence of the latter is exceedingly low.
Autosomal dominant and recessive disease is caused by a myriad of different mutations affecting various structural components and enzymatic processes of connective tissue making it difficult to discuss these as a single entity. Therefore, the following content will be limited to acquired cutis laxa.
Characteristic findings on physical examination
The typical presentation of acquired cutis laxa is that of loose, sagging skin. Loss of resilience in the dermis causes the skin to succumb to gravity. In the most simplistic view, aging of the skin through internal and external causes could be considered an acquired variant of cutis laxa. The most striking finding of skin aging is dermatochalasis, the progressive hooding of the upper lids, and jowl formation along the jaw line. The term acquired cutis laxa is however reserved to describe degenerative changes of the skin that follow events other than aging or extensive sun exposure.
Acquired cutis laxa type I refers to an onset of skin changes mostly in adulthood, affecting both men and women equally. When skin involvement is localized, systemic findings are absent. However, with generalized skin changes there is a greater likelihood to encounter systemic manifestations similar to those seen in the congenital variants. Pulmonary emphysema, aortic ectasia, cor pulmonale, and hernias affecting the abdominal wall, the digestive or urogenital system may develop.
Acquired cutis laxa type II, also referred to as Marshall syndrome, affects infants or children with a slight female preponderance. It had first been decribed in African infants and toddlers but has since been reported in variable ethnic settings. In type II, loss of elasticity of the skin is localized and almost always involves the face and neck whereas systemic findings are absent.
Expected results of diagnostic studies
The characteristic feature under light and electron microscopic examination is fragmentation and loss of elastic fibers in the mid dermis. Occasionally, alterations in the collagen network are observed; however, this is believed to be due to changes in the mechanical properties within the dermis. Genetic testing does not apply to acquired cutis laxa, however, missense alleles in the elastin and fibulin 5 genes may be predisposing factors. Tests for the various genes underlying the rare types of heritable cutis laxa may be commercially available in the future.
Anetoderma is usually classified as a distinct disorder of round patches of dermal atrophy and loss of recoil. By some, anetoderma is considered a variant of localized acquired cutis laxa type II, namely Marshall Syndrome, because the histopathologic changes are identical. Differential diagnosis for generalized acquired cutis laxa type I includes autosmal dominant cutis laxa with delayed onset. A family history of cutis laxa will help distinguish the condition, if present. While mutation analysis of the elastin or fibulin 5 genes may be considered in the absence of a family history, it may have no merit, as clinical management is the same.
Some forms of Ehlers Danlos syndrome are characterized by very loose skin. However, recoil is not missing and skin fragility is a striking feature not seen in cutis laxa. Pseudoxanthoma elasticum with vitamin K dependent coagulation factor deficiency displays severe skin laxity yet histopathologic examination will reveal calcium deposits around fractured elastic fibers in the dermis. Mid dermal elastolysis typically causes fine wrinkling of the upper arms and upper back in conjunction with sun damage.
Who is at Risk for Developing this Disease?
There are no known risk factors for acquired cutis laxa. However, the presence of missense alleles in the elastin and fibulin 5 genes in some patients gives rise to speculations about a genetic predisposition without evidence of racial or gender prediliction.
What is the Cause of the Disease?
The etiology of acquired cutis laxa type I and type II remains elusive. Type I predominantly affects adults and may occur spontaneously or after an inflammatory condition. The latter comprise a wide range of events, including idiopathic inflammation and allergic or other reactions to medicines such as penicillin, isoniazide and D-penicillamine. Further preceding factors are hematologic abnormalities like plasma cell dyscrasias and congenital hemolytic anemia, which causes localized acral cutis laxa, as well as infections, especially Borrelia burgdorferi. Other inciting inflammatory disorders like urticaria, angioedema, rheumatoid arthritis, systemic lupus eythematosus, erythema multiforme, nephrotic syndorme, celiac disease and dermatitis herpetiformis have been reported. Finally, it has been associated with paraneoplasia.
Type II (Marshall syndrome) occurs in infants and toddlers and develops in response to acute inflammatory skin lesions. Rare associations with alpha 1 antitrypsin deficiency, arthropod bites and Sweet’s syndrome have been described.
Degradation of elastic fibers through proteolyitc processes is believed to play a role in acquired cutis laxa. This concept is supported by the presence of tissue elastases released after activation of polymorphonuclear leukocytes and monocyte-macrophages in an inflammatory event. IgG and IgA deposits in lesional skin and paraproteinemia have also been reported and raise the possibility of an immunopathogenetically mediated process.
Systemic Implications and Complications
The following systemic organ involvement may occur in acquired cutis laxa type I when disease affects the skin in a generalized manner:
Inguinal and umbilical hernias
Gastrointestinal amd urogenic diverticulae
Treatment options for acquired cutis laxa include:
Plastic reconstructive surgery
Laser skin tightening (only minimally effective)
Treatment for internal complications
Optimal Therapeutic Approach for this Disease
The skin changes do not mandate specific physical considerations but can pose an enormous psychosocial burden by causing a prematurely aged appearance. Although systemic involvement and complications are rare, these need to be treated adequately. Reversal of cutis laxa with treatment of a systemic association has not yet been reported.
If an inciting event is known that has led to the development of cutis laxa; avoidance of reexposure (in case of medications) is recommended.
Unusual Clinical Scenarios to Consider in Patient Management
Although paraneoplastic aquired cutis laxa is rare, any such evaluation should focus on the possible association of myeloma or myelodysplasia.
An unusual rare variant of acquired cutis laxa may have lesions limited to the face unassociated with any systemic implications or prior inflammatory lesions.
What is the Evidence?
Marshall, J, Heyl, T, Weber, HW. “Post inflammatory elastolysis and cutis laxa”. South Afr Med J. vol. 40. 1966. pp. 1016-22. (This is a report of African infants with cutis laxa and anetoderma that developed within areas of preceding urticaria or inflammatory papules).
Shapiro, SD. “Matrix metalloproteinase degradation of extracellular matrix: biological consequences”. Curr Opin Cell Biol. vol. 10. 1998. pp. 602-8. (Review of the role of proteolytic fragments of extracellular matrix proteins in regulating a variety of critical processes in cell biology.)
Krajnc, I, Rems, D, Vizjak, A, Hodl, S. “Acquired generalized cutis laxa with paraproteinemia (IgG lambda). Immunofluorescence study, clinical and histologic findings with review of the literature”. Hautarzt. vol. 47. 1996. pp. 545-9. (Case report of a patient who developed acquired generalized cutis laxa with pulmonary emphysema, esophageal diverticulae and inguinal hernias. Histopathologic changes included IgG lambda chain deposits along preserved elastic fibers in the papillary dermis.)
Hu, Q, Reymond, J-L, Pinel, N, Zabot, MD, Urban, Z. “Inflammatory destruction of elastic fibers in acquired cutis laxa is associated with missense alleles in the elastin and fibulin-5 genes”. J Invest Dermatol. vol. 126. 2006. pp. 283-90. (This is a report of a single patient with acquired generalized cutis laxa in whom missenes changes in the elastin and fibulin 5 genes caused functional impairment in proteolytic processing of tropoelastin and increased deposition of insoluable elastin, respectively.)
Mehta, R, Amladi, S. “Acquired localized cutis laxa of the face: A rare presentation”. Pediatr Dermatol. vol. 28. 2011. pp. 421-3. (A case report of a 16-year-old boy with de novo acquired localized cutis laxa of the face, unaccompanied by any preceding inflammatory lesions, or systemic associations, and a review of five similar cases.)
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.