Dermatologists cannot be lax about acquired cutis laxa
By Warren R. Heymann, MD
Jan. 28, 2019
From the time I was a medical student, I have always been fascinated by the “little old man” appearance of patient with cutis laxa (CL).
In their excellent review, Berk et al note that CL is characterized by abnormal elastic fibers resulting in loose, redundant skin. Typically, skin in CL can easily be pulled and only slowly returns to its original position. Unlike some conditions in the differential diagnosis, notably Ehlers-Danlos syndrome(s) or pseudoxanthoma elasticum, easy bruising or abnormal scarring does not characterize CL. Redundant skin is often most noticeable on the neck, hands, and groin, but can also be seen on the face, creating a premature aging appearance.
CL may be inherited or acquired (ACL). Inherited forms include autosomal dominant CL; autosomal recessive CL (ARCL)-I, -IIA, and -IIB; X-linked CL and other variants. Although all of the inherited forms of CL are rare, ARCL has most commonly been reported, particularly ARCL-II. Because of significant overlap among these types, precise clinical classification can be difficult. For the clinical differentiation of the variants and their genetic mutations, please refer to Berk et al (1).
The etiology of CL involves abnormalities the elastic fiber network in skin and internal organs. Autosomal dominant CL has been associated with mutations of the elastin gene. X-linked CL is associated with gene mutations ATPA7 and abnormalities of copper transport. The autosomal recessive forms of CL are heterogeneous. Type 1 is associated with mutations in the gene encoding fibulin 5. Type 2 is associated with mutations in the lysyl oxidase gene. Acquired cutis laxa can follow many conditions increasing the degradation of elastic fibers. (2)
This commentary will focus on new information regarding ACL, which is more common than the inherited forms of CL (albeit still rare — I have only encountered such cases at conferences).
As an illustrative case, Kim et al reported a 54 year-old man with pendulous, inelastic skin of the face, neck, shoulders and trunk, of 7 years duration. Skin biopsies demonstrated decreased and fragmented elastic fibers with Verhoeff stain. Genetic studies ruled out an Ehlers-Danlos syndrome. Approximately 5 years prior to his presentation, he was diagnosed with pancreatic cancer, prostate cancer, and thyroid cancer. Although his malignancies have not been reported with ACL (3), a paraneoplastic effect causing elastic degradation, possibly from pancreatic enzymes, seems plausible in this case.
ACL has an insidious onset most often occurring in adulthood. ACL may be associated with various disorders and drugs (see Table II from Berk et al in the addendum). ACL often starts on the face and progresses caudally. Some patients have systemic involvement with emphysema, intestinal diverticulae, hernias, and vascular dilatations. Approximately 50% of cases are associated with an inflammatory dermatosis (1) Mechanistically, excessive elastase activity from neutrophils and macrophages, an immune-mediated mechanism, or a dysfunction in elastase inhibitors may be at play in affecting the elastic fibers. (4)
ACL is classified into two types: Type I ACL occurs mainly in adults and progresses cephalocaudally as described above. Internal involvement occurs often. Type 2 ACL usually presents in children, with limited skin involvement; internal organ disease only occurs rarely. (3)
Jachiet et al performed a retrospective multicenter study including 14 patients (9 men and 5 women, mean age 56 years) with ACL, loss of elastic fibers on skin biopsy, and a detected monoclonal gammopathy (MG). Three patients had multiple myeloma, 1 smoldering multiple myeloma, 6 MG of unknown significance, and 4 heavy-deposition disease (HCDD). Systemic manifestations related to elastic fiber destruction included pulmonary emphysema in 8 cases (57%), digestive involvement in 6 cases (43%), and genitourinary involvement in 1 case. The 4 patients with HCDD had hypoalbuminemia, hypocomplementemia, and specific renal involvement (membranoproliferative glomerulonephritis [n = 1] or nodular glomerulosclerosis [n = 3]. The authors concluded that the pathogenic role of a small immunoglobulin-producing clone in ACL could be included in the spectrum of MG with cutaneous significance. (5)
To date, there appears to be no effective treatment for ACL – by the time the diagnosis has been rendered, elastin damage has already occurred. Perhaps the earlier the diagnosis is considered, treating the associated disorder (if any) aggressively makes sense. I can only imagine the psychological devastation that accompanies ACL. Referral to plastic surgery is warranted. Perhaps future pharmacological interventions specifically targeted for tissue elastases and their inhibitors can be devised. Until such time, dermatologists cannot be lax in their assessment and management of patients with ACL.
Point to remember: Patients with acquired cutis laxa require a careful review of systems focusing on the lungs, GI, and GU tracts. Don’t forget to check a serum protein electrophoresis for a monoclonal gammopathy.
Berk DR, et al. Cutis laxa: A review 2012; 66: 842 e 1-17.
Gara S, Litaiem N. Cutis laxa (Elastolysis). StatPearls (Internet). Treasure Island (FL): StatPearls Publishing 2018-2018 Nov 6.
Kim SM, et al. A case of generalized cutis laxa. Int J Dermatol 2018; 57: 1369-71.
Paulsen IF, et al. Acquired cutis laxa: Diagnostic and therapeutic considerations. J Plast Reconstr Aesthet Surg 2014; 67: 242-3.
Jachiet M, et al. Cutis laxa associated with monoclonal gammopathy: 14 new cases and review of the literature. J Am Acad Dermatol 2018; 79: 945-7.
Addendum: Disorders and Medications Associated with ACL (adopted from Reference 1)
Sweet syndrome (Marshall syndrome)
Connective tissue diseases
Systemic lupus erythematosus
Alpha-1 antitrypsin deficiency
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