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. 2023 Feb 28;188(6):800–816. doi: 10.1093/bjd/ljad043

Clinical features in adults with acquired cutis laxa: a retrospective review

Katie A O’Connell 1,2, Morgan Schaefer 3, Lihi Atzmony 4,5,6, Ruth Ann Vleugels 7, Keith Choate 8, Avery H LaChance 9, Michelle S Min 10,11,✉,b,c
PMCID: PMC10230959  PMID: 36849736

Abstract

Acquired cutis laxa (ACL) is a very rare dermatological condition with numerous proposed aetiologies. Herein, we report on 10 adult patients with ACL, three of which were found to have genetic mutations suggesting a genetic predisposition for the development of ACL following exposure to an environmental insult. Four patients were presumed to develop ACL in association with medication exposure. Overall, if a case of potential ACL arises, providers should carefully review patient history and comorbidities, perform thorough systemic investigations based on symptomatology, and consider genetic analysis.


Dear Editor, Acquired cutis laxa (ACL) is a rare dermatological condition with numerous proposed aetiologies including medications, malignancy, infection, enzyme disorders, autoimmunity and renal disease, and although the pathogenesis of inherited CL is somewhat understood, little is known about ACL.1 ACL is presumed to be a sequela of environmental exposures leading to elastic fibre destruction.2 ACL typically presents in adulthood, and diagnosis is based on history and clinical examination followed by histopathology revealing reduction in elastic fibres or elastic fibre fragmentation.2,3 Patients have localized or generalized wrinkled skin, and disease is either insidious or associated with preceding inflammation.1,2 This study aimed to better understand potential presentations and triggers of ACL.

Following approval by the Institutional Review Board at Mass General Brigham (MGB), patients diagnosed with CL from January 1989 to April 2021 at MGB hospitals were identified using the Research Patient Data Registry. Inherited CL was excluded. Data were then extracted from medical records.

Ten adults (6 of 10 females) with ACL were identified with an average age at diagnosis of 40 (range 21–69) years (Table 1). As expected, skin laxity was seen in all patients. A majority was found to have additional cutaneous features such as dyspigmentation or pruritus (Table 1). Leading areas of involvement were upper extremities (6 of 10), lower extremities (5 of 10), face (5 of 10) and abdomen (5 of 10). Nine of ten patients underwent skin biopsy. Six patients received genetic testing (three whole-exome sequencing, one whole-genome microarray, two CL panels, one Ehlers Danlos panel, one cystic lung disease panel, one connective tissue disease panel, one single-gene analysis), three of which returned positive. All three patients had associated systemic manifestations: pulmonary disease (alpha-1 antitrypsin); abdominal hernia, obstructive lung disease and coagulopathy (GGCX); and refractory hypertension, visual deficits and leucopenia (LTPB4/ALDH18A).

Table 1.

Characteristics of patients diagnosed with acquired cutis laxa

Age at diagnosis (years), sex, race/ethnicity, years since CL diagnosis Comorbidities Cutaneous manifestationsa Areas of skin involvement Systemic involvement Treatment and outcome Specialists other than Dermatology Genetic testing (results) Suspected inciting event or medication
52, M, Black, 8 Sjogren syndrome, cutaneous lupus, HTN, type 2 diabetes mellitus Skin laxity-associated paraesthesia, hyperpigmentation Cheeks, forearms, hands, buttocks, thighs None None Rheumatology, gastroenterology, endocrinology, genetics LMNB2 gene (negative)
29, M, White, 1 Leucocytoclastic vasculitis with renal involvement, chronic idiopathic urticaria Skin laxity, associated striae Face, neck, axillae, abdomen None None Allergy, rheumatology None Leucocytoclastic vasculitis
23, F, White, 2 None Skin laxity Breasts, thighs, hips, legs None None Rheumatology, genetics, gastroenterology, breast oncology, infectious diseases WES, CL panel, Ehlers Danlos panelb (negative) Amoxicillin
69, F, White, 5 Asthma, irritable bowel syndrome, carpal tunnel, spinal stenosis, panic disorder Skin laxity and wrinkling Lower face, upper extremities, bilateral thighs Obstructive pulmonary disease None Pulmonology, cardiology, haematology/oncology, genetics Cystic lung disease panelc
[MZ carrier at SERPINA1 (alpha-1 antitrypsin)]
54, M, White, 1 Frontal fibrosing alopecia, lichen planus, anxiety, hypothyroidism, lumbosacral radiculopathy, peripheral venous insufficiency, GERD Skin laxity Face, upper and lower extremities None None None None
45, F, White, 12 Asthma, sinusitis, pulmonary disease with eosinophilia and elevated IgE Skin laxity, hypopigmentation (specifically on neck) Neck, upper extremities (most pronounced on shoulders, antecubital fossa), upper chest, back, abdomen None Prednisone, dapsone, ciclosporin, PUVA (no improvement), Fraxel laser (improved) None None Escitalopram
34, M, Black, 4 HTN, multiple myeloma Skin laxity Face (most pronounced on upper/lower eyelids), neck, upper extremities, back, abdomen None Bilateral upper blepharoplasty, rhytidectomy, midface lift, neck lift (minimal improvement) Genetics, otolaryngology, haematology/oncology Whole-genome microarray (negative) Multiple myeloma
25, F, White, 7 None Skin laxity, pruritus, oedema, erythema Right upper back None Clobetasol, tacrolimus (improved) None None Levonorgestrel-releasing intrauterine device
21, F, White, 2 Raynaud phenomenon Skin laxity Neck, proximal upper extremities, back, abdomen Obstructive pulmonary disease, abdominal hernia, coagulopathy Bilateral brachioplasty and neck lift (improved), Fraxel laser for abdomen (improved) Genetics, cardiology, pulmonology, plastic surgery, ophthalmology WES (compound het. GGCX c.2017C > T, p.R673X, c.763G > A, p.V255M mutations) Sertraline
45, F, Asian, 8 None Skin laxity Chest, back, abdomen, lower extremities Refractory HTN, bilateral renal artery stenosis, leucopenia, iron deficiency anaemia, visual deficits NB-UVB, prednisone (no improvement) Vascular surgery, cardiology, pulmonology, genetics, gastroenterology, nephrology WES, CL panel, CTD panel (het. LTBP4 mutation c.1307G > A, R436H, het. ALDH18A1 c.1222G > A, R41H mutation)

CL, cutis laxa; CTD, connective tissue disease; GERD, gastroesophageal reflux disorder; het., heterozygous; HTN, hypertension; IgE, immunoglobulin E; NB-UVB, narrowband ultraviolet B; PUVA, psoralen with ultraviolet light A; WES, whole-exome sequencing.

a

Associated with areas of CL skin involvement as listed in column only unless otherwise noted. bCutis laxa panel: ALDH18A1, ATP6V0A2, EFEMP2, ELN, FBLN5, LTBP4, PYCR1; Ehlers Danlos panel: ADAMTS2, ATP7A, B3GALT6, B4GALT7, CHST14, COL12A1, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, CRTAP, FKBP14, FLNA, P3H1, PLOD1, SLC39A13. cCystic lung disease panel: EFEMP2, ELN, FBLN5, FLCN, LTBP4, SERPINA1, TSC1, TSC2.

Almost half the patients (4 of 10) were presumed to have developed ACL in association with medications, two of these being selective serotonin reuptake inhibitors (SSRIs).3 Suspected drugs were escitalopram, sertraline, amoxicillin and a levonorgestrel-releasing intrauterine device (IUD). Two patients were suspected to have developed ACL associated with medical comorbidities, leucocytoclastic vasculitis and multiple myeloma. Half (5 of 10) sought treatment. One patient with focal disease noted improvement following 5 months of topical therapy (clobetasol, tacrolimus). Three noticed moderate improvement with lasers, surgery, or both. The data underlying this article cannot be shared publicly due to the Health Insurance Portability and Accountability Act. This project was approved by the Institutional Review Board at Mass General Brigham (#2021P000222).

Drugs (penicillin, penicillamine, isoniazid) have been associated with ACL; herein we add a second case of SSRI-associated CL, the first also reported from MGB.3 No cases following IUD placement or antibiotic therapy have been reported, although our patient on antibiotics was empirically being treated for Borrelia burgdorferi, which has been associated with ACL.1–3 In line with previous reports, clinical evidence of CL may develop gradually, as in the case of our patients receiving SSRI therapy, or suddenly, as in the case of the patient following IUD placement. It is recommended to discontinue the potentially offending medication to prevent further damage; however, degenerative dermal changes resulting from CL are generally irreversible.4 Monoclonal gammopathy and leucocytoclastic vasculitis have both been previously associated with ACL diagnoses.2,5 Although larger studies are warranted, providers should be aware of these potential associations and thoroughly review medications.

Reports of gene mutations in cases of ACL are exceedingly rare.1–3,6 However, our cohort identified three patients. We hypothesize these cases might have arisen in adulthood in individuals with underlying genetic mutations associated with CL who subsequently were exposed to another environmental insult.6 If a case of potential ACL arises, we recommend careful review of patient history and comorbidities. Thorough systemic investigations based on symptomatology should be considered for all patients with ACL, given the increased likelihood of associated systemic involvement, including cardiovascular, pulmonary and gastrointestinal disorders.2 Notably, patients with or without systemic involvement may have genetic susceptibility for CL development. Genetic analysis with a CL panel should be considered, and those with unexplained systemic symptoms may warrant whole-exome sequencing should initial analyses return normal.

In line with prior studies, few patients in our series reported improvement following immunomodulators, with one patient improving following topical clobetasol and tacrolimus.2 Similarly, procedural approaches may provide modest benefit in some patients, although patients should be counselled that multiple treatments may be necessary and disease progression will not be impacted.2,7 While the retrospective nature and size of our study are limitations, ACL is extremely rare, with few reported series. Further studies are warranted to explore ACL aetiology and genetic susceptibility.

Contributor Information

Katie A O’Connell, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Morgan Schaefer, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

Lihi Atzmony, Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA; Division of Dermatology, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Ruth Ann Vleugels, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

Keith Choate, Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.

Avery H LaChance, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.

Michelle S Min, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Department of Dermatology, University of California Irvine School of Medicine, Irvine, CA, USA.

Funding sources

The genetic analysis was supported in part by the National Institutes of Health (R01 AR071491) and the Yale Center for Mendelian Genomics (U54 HG006504/HG/NHGRI NIH).

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Articles from The British Journal of Dermatology are provided here courtesy of Oxford University Press

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