Abstract
Background: Acquired cutis laxa (ACL) is an uncommon dermatological condition characterized by loose, inelastic skin due to the degradation of elastic fibers. Traditionally studied within dermatology, recent insights have highlighted significant associations with hematological disorders, particularly monoclonal gammopathies.
Objective: This commentary extends the discussion presented in the review article "Acquired cutis laxa: a clinical review" by Khodeir et al., emphasizing recent advancements in the understanding of ACL’s hematological connections. It focuses on paraneoplastic associations and their treatment, alongside a newly documented case linking ACL with IgA gammopathy.
Methods: A comprehensive review of recent literature and new cumulative data on ACL associated with neoplastic disorders was conducted. A detailed case report illustrates the clinical and pathological findings of ACL associated with IgA lambda paraproteinemia.
Results: Among 110 patients reviewed, 30 cases (27%) were linked to paraneoplastic disorders, primarily multiple myeloma and monoclonal gammopathy of undetermined significance. ACL typically preceded the diagnosis of these conditions by an average of 2.4 years. The newly reported case of ACL with IgA gammopathy further reinforces the link between ACL and monoclonal gammopathies. The pathogenesis involves complex mechanisms including enzymatic degradation of elastic fibers, immunoglobulin-mediated elastolysis, and chronic inflammation.
Conclusion: ACL presents a dermatological challenge increasingly linked to hematological disorders, particularly monoclonal gammopathies. Recognizing ACL as a potential paraneoplastic marker underscores the need for thorough hematological evaluation and long-term follow-up in patients. Continued research into the pathogenesis and therapeutic strategies is crucial for improving clinical outcomes and refining management guidelines for ACL.
Keywords
Acquired cutis laxa, Acquired elastolysis, paraneoplastic skin changes, Monoclonal gammopathy of cutaneous significance
Introduction
Acquired cutis laxa (ACL) is a rare dermatological disorder characterized by loose, sagging, and inelastic skin due to the progressive degradation of elastic fibers within the dermis. Unlike the congenital form of cutis laxa, which is present from birth and often linked to genetic mutations, ACL typically develops later in life and can be associated with various underlying conditions. Patients with ACL may notice that their skin appears prematurely aged and lacks elasticity, often manifesting as either a generalized form affecting the entire body or a localized form impacting specific areas [1]. While the exact cause of ACL remains unclear, it is thought to result from several factors such as inflammatory diseases or autoimmune disorders, neoplastic disorders, infections, or drugs that lead to the destruction of elastic fibers [2]. While the primary focus of ACL has traditionally been within dermatology, recent insights have highlighted significant associations with hematological disorders, particularly monoclonal gammopathies [2]. This commentary extends the discussion presented in the review article "Acquired cutis laxa: a clinical review" by Khodeir et al., emphasizing recent advancements in the understanding of ACL’s hematological connections, with a particular focus on paraneoplastic associations and their treatment, in addition to a newly documented case in the literature linking ACL with IgA gammopathy.
Paraneoplastic Associations
The review by Khodeir et al. outlines various systemic associations of ACL. However, it is important to highlight the significant link between ACL and hematological malignancies at the outset of this discussion. ACL can serve as a cutaneous marker for underlying malignancies, particularly monoclonal gammopathies [2]. The spectrum of monoclonal gammopathies includes conditions such as multiple myeloma, Waldenström’s macroglobulinemia, monoclonal gammopathy of renal significance, and monoclonal gammopathy of undetermined significance (MGUS). These conditions can manifest with cutaneous symptoms, including ACL, underscoring the critical need for clinicians to recognize ACL as a potential indicator of serious underlying hematological disorders [3].
Patient Demographics and Associations
The review analyzed 110 patients with ACL [2]. Key demographics and associations are summarized in Table 1.
|
Category |
Results |
|
Total Number of Patients |
110 |
|
Mean Age |
36.4 years |
|
Male-to-Female Ratio |
1.24 |
|
Associations |
|
|
43% |
|
27% (30 cases) |
|
50% (15 cases) |
|
30% (6 cases) |
|
10% (6 cases, including light and heavy chain deposition disease) |
|
6.6% (2 cases, cutaneous lymphoplasmacytic lymphoma and cutaneous angiocentric T-cell lymphoma) |
|
0.3% (1 case) |
|
10% |
|
2% |
|
2% |
|
16% |
In contrast to inflammatory cases, ACL typically preceded the diagnosis of multiple myeloma (MM), MGUS, and monoclonal gammopathy of renal significance (MGRS) by an average of 2.4 years in the majority of patients (73%, 22 out of 30 cases). Generalized ACL was observed in the majority of patients in this group (83%), with acral localization seen in 17% of patients [2].
Case Report: ACL and IgA Gammopathy
A recent case report by Zhang et al. [4] describes a 62-year-old male with ACL who was found to have IgA lambda paraproteinemia. The patient was initially presented with diffuse skin laxity and developed systemic symptoms, including pulmonary emphysema. Skin biopsy confirmed ACL, and serum and urine electrophoresis revealed IgA lambda paraprotein. Notably, the ACL preceded the diagnosis of IgA gammopathy by two years, highlighting the need for thorough hematological evaluation and long term follow up in patients with ACL, even without immediate hematological symptoms. This aligns with the findings of Khodeir et al., who showed that ACL can occur an average of 2.4 years before diagnosing an underlying hematologic neoplastic disorder.
New Cumulative Data on ACL and Neoplastic Disorders
After including the recent case by Zhang et al., the total number of reported cases associated with an underlying neoplastic disorder increased to 31. Of these, 18 were males and 13 females, with a mean age of 47.25 years. In 23 out of 31 cases (74%), ACL occurred years before the development and diagnosis of a neoplastic disorder, with an average onset of 2.4 years prior. All cases associated with an underlying neoplastic disorder are summarized in Table 2.
|
Study identifier |
Study design |
Number of patients |
Age and sex |
Clinical presentation |
Histology |
Associated disease |
Time of appearance of laxity |
Treatment |
Outcome |
|
Appiah et al. [12] |
case report |
1 |
64, female |
acral localized on finger tips |
diminution of elastic fibers in the dermis, focal clumping of the elastic fibers around vessels |
Multiple myeloma (MM) and amyloidosis |
3 years before MM |
NA |
NA |
|
Jain [56] |
case report |
1 |
34, male |
laxity on face, neck, and bilateral axillary folds |
loss of elastic fibers in the upper dermis |
monoclonal gammopathy of renal significance (MGRS) |
3 years before MGRS |
NA |
No improvement in laxity |
|
Yadav et al. [37] |
case report |
1 |
44, female |
laxity on the face, earlobes and neck |
short and fragmented elastic fibers in the upper dermis with granular degeneration |
MM |
2 years after diagnosis |
plastic surgery |
patient followed for 4 years, no laxity after surgery |
|
Tan et al. [31] |
case report |
1 |
50, male |
generalized loose skin |
loss of elastic fibers in the superficial and deep dermis. Electron microscopy revealed fragmented and clumped elastic fibers, with IgG deposition around elastic fibers |
heavy chain deposition disease |
4 years after diagnosis |
plastic surgery |
good outcome after surgery no recurrence |
|
Turner et al. [8] |
case report |
1 |
29, male |
laxity on the face, neck, axillae, shoulders, arms and abdomen |
loss of elastic fibers is seen surrounding vessels involved by leukocytoclastic vasculitis |
urticarial vasculitis associated with IgA myeloma |
1 year after urticarial lesions, 1 year before myeloma diagnosis |
NA |
bad prognosis, patient passed away without specific treatment |
|
Shalhout et al. [28] |
case report |
1 |
35, male |
laxity of the periocular skin, neck, axillary, and back |
perivascular lymphocytic inflammation with rare giant cells, decreased elastic fibers in the reticular dermis |
Monoclonal gammopathy of dermatological significance |
1 year before diagnosis of gammopathy |
systemic steroids and immunosuppressive therapy |
no progression in laxity after 1 year |
|
Machet et al. [30] |
case report |
1 |
34, male |
laxity on the eyelids then became generalized |
fragmentation shortening and clumped elastic fibers, lambda IgG binding to microfibrillar component of elastic fibers |
IgG lambda Monoclonal gammopathy |
2 years before diagnosis of gammopathy |
NA |
NA |
|
Kluger et al. [13] |
case report |
1 |
40, male |
acral localized, on fingers bilaterally |
diminution of the elastic fibers with elastophagocytosis. IgA deposits at the dermoepidermal junction |
IgA Multiple Myeloma, Urticarial Neutrophilic Dermatosis |
after urticaria |
methotrexate, colchicine, hydroxychloroquine, intravenous gammaglobulins and dapsone |
did not prevent the progression in skin or joint laxity |
|
Callen et al. [46] |
case report |
1 |
48, male |
laxity of his face, chest, upper back, lateral hips, buttocks, and proximal upper extremities |
elastic fiber fragmentation in dermis |
MM |
8 years before MM |
lenalidomide, dexamethasone, pamidronate |
progression of laxity despite treatment of MM |
|
Kim et al. [47] |
case report |
1 |
55, female |
generalized skin laxity |
interstitial foamy macrophages, diminished elastic fibers in reticular dermis |
MM/SLE |
7 years before MM |
bortezomib and dexamethasone then IVIG and danazol |
no progression in laxity |
|
Majithia et al. [50] |
case report |
1 |
40, male |
laxity on face, neck axilla and trunk |
marked reduction in elastic fibers in the superficial and deep reticular dermis |
light and heavy chain deposition disease |
1 year before appearance of LHCDD |
systemic steroids and cyclophosphamide |
laxity remained without further progression |
|
de larrea et al. [33] |
case report |
1 |
52, male |
laxity of body folds, neck and axilla |
reduction of the number of elastic fibers throughout the dermis |
IgG lambda monoclonal gammopathy |
2 years before diagnosis |
bortezomib ⁄ dexamethasone |
no progression in laxity |
|
Lee et al. [48] |
case report |
1 |
54, female |
lax skin on the thumbs, with periorbital purpura |
reduction and fragmentation of elastic fibers in the reticular dermis |
Primary systemic amyloidosis and MM |
1 year before diagnosis |
Bortezomib, thalidomide and dexamethasone followed by autologous peripheral stem cell transplantation |
Slight improvement |
|
Nikko et al. [26] |
case report |
1 |
40, female |
laxity on trunk, neck and proximal extremities |
fragmentation and a marked reduction in elastic fiber in the dermis, prominent elastophagocytosis by histiocytes |
Plasma cell dyscrasia |
1 year before diagnosis |
NA |
NA |
|
Gupta et al. [51] |
case report |
1 |
62, female |
laxity face, neck, chest, and back |
loss of elastic fibers |
MM |
5 years after |
vincristine, melphalan, doxorubicin, cyclophosphamide, and prednisone |
NA |
|
González Rodríguez et al. [27] |
case report |
1 |
54, male |
laxity of the face and flexures (neck, armpits, groin, abdomen) |
significant reduction and fragmentation of elastic fibers and elastophagocytosis |
monoclonal gammopathy of uncertain significance (MGUS) and lambda light chain deposition disease |
5 months before MGUS diagnosis |
bortezomib and dexamethasone with dialysis |
patient passed away |
|
Lavorato et al. [49] |
case report |
1 |
57, female |
laxity on face neck upper trunk |
fragmentation of elastic fibers |
Primary systemic amyloidosis, cutaneous mucinosis, multiple myeloma |
3 years after hyperchromia but 7 years before diagnosis of MM and amyloidosis |
Bortezomib and Dexamethasone, autologous bone marrow transplantation, 2 blepharoplasties |
no progression after treatment of MM |
|
Silveira et al. [57] |
case report |
1 |
29, male |
laxity on face, axillae, groin, and neck |
elastophagocytosis and loss and fragmentation of elastic fibers |
IgG Lambda Monoclonal Gammopathy (MGUS) |
1 year before diagnosis |
NA |
NA |
|
Gonzalez-Ramos et al. [9] |
case report |
1 |
68, male |
lax and redundant skin at the axilla and antecubital flexure. |
multinucleated giant cells with elastophagocytosis |
MGUS then MM |
4 years before MGUS Diagnosis |
NA |
NA |
|
Ferrandiz pulido et al. [58] |
case report |
1 |
63, male |
laxity on all fingertips of the hands |
eosinophilic material in dermis positive with Congo red. elastic tissue fragmentation and diminution in dermis |
multiple myeloma-associated amyloidosis |
3 months before diagnosis |
NA |
NA |
|
Moretta et al. [59] |
case report |
1 |
39, female |
generalized laxity |
clustered or fragmented elastic fibers |
?-chain IgA micromolecular myeloma |
1 year before diagnosis of myeloma |
Dapsone |
chemotherapy for MM led to stabilization on laxity |
|
Dong Jun Lim et al. [53] |
case report |
1 |
45, female |
laxity over the axilla and back. |
diffuse infiltration of lymphocytes and plasma cells. Elastophagocytosis was observed in the dermis |
cutaneous lymphoplasmacytic lymphoma |
3 years before diagnosis |
chemotherapy (CHOP, Bendamustine/Rituximab) |
lax skin did not improve |
|
O’Connell et al. [60] |
retrospective review |
10 |
34, male |
skin laxity Face (most pronounced on upper/ lower eyelids), neck, upper extremities, back, abdomen |
fragmented to absent elastic fibers |
MM |
years after |
plastic surgery |
NA |
|
Chartier et al. [61] |
case report |
1 |
64, male |
generalized wrinkling affecting the whole body |
mild dermal perivascular inflammatory infiltrate with a predominance of mononuclear cells marked by a net reduction in elastic fibers throughout the dermis |
cutaneous angiocentric T-cell lymphoma |
1.5 years after diagnosis |
NA |
NA |
|
Hinek et al. [62] |
case report |
1 |
35, female |
generalized elastolysis |
elastic fibers were structurally abnormal and lacked fibrillin-1 |
monoclonal gammopathy |
NA |
dexamethasone and losartan |
potent deposition of fibrillin-1 microfibrils and restored production of normal elastic fibers |
|
New et al. [63] |
case report |
1 |
48, male |
loose, redundant skin on the face, upper trunk, and axillae |
scant histiocytic infiltrate with mid-dermal elastolysis |
MM |
4 years before dx of mm |
NA |
NA |
|
Galiczynski et al. [52] |
case report |
1 |
51, female |
generalized skin laxity |
absence of elastic fibers within the papillary dermis |
MGRS |
1 year before diagnosis |
prednisone, melphalan, rituximab, and cyclophosphamide |
progressed into renal failure, cardiac and pulmonary involvement without response on therapy |
|
Bennassar et al. [32] |
case report |
1 |
52, male |
generalized skin laxity |
complete depletion of elastic fibers, IgG deposition on fragmented dermal elastic fibers |
MGRS |
2 years after |
bortezomib and dexamethasone |
no further progression in skin laxity |
|
Van Meurs et al. [64] |
case report |
1 |
51, male |
laxity of the face, the neck and extremities |
loss of dermal elastic tissue |
MGUS |
1.5 year before MGUS |
NA |
NA |
|
Cho et al. [11] |
case report |
1 |
46, female |
generalized cutaneous and systemic elastolysis including lungs and heart |
fragmentation of elastic fibers with IgG bound to elastic fibers |
MM |
around a year before |
oral steroids |
patient died due to systemic involvement |
|
Zhang et al. [4] |
letter to editor |
1 |
48, female |
generalized skin laxity with lung involvement |
absent elastic fibers, infiltration of mononuclear cells, foam-like cells, occasional eosinophils, and giant cells in the dermis |
IgA lambda monoclonal gammopathy of cutaneous significance |
2 years before diagnosis |
anti-plasma cell therapy |
NA |
Clinical Manifestations of ACL
Clinically, ACL manifests in two main types [1]. Type II ACL, also referred to as Marshall syndrome, primarily affects pediatric patients, characterized by localized skin laxity and often associated exclusively with conditions like Sweet syndrome or other neutrophilic dermatoses [5]. Type I ACL, which is the focus here, can be linked to underlying neoplastic disorders in adults, as reported in 27% of cases [2]. In Type I ACL, systemic involvement may affect multiple organ systems, including cardiovascular, pulmonary, urogenital, and gastrointestinal systems [1]. Patients with systemic involvement exhibit a high mortality rate (6 out of 19 cases succumbed to the disease) [6-11]. When generalized, lesions typically initiate on the face, progressing cephalocaudally to involve skin folds such as the axilla, inframammary region, inguinal area, and trunk [1,2]. Localized lesions may occur on the palms, fingers, and soles, known as acral localized [12,13].
Pathogenesis of ACL
The pathogenesis of ACL involves several interconnected mechanisms. It includes:
Enzymatic degradation of elastic fibers
This mechanism occurs by direct degradation by neutrophil elastases or indirectly via deficiencies in elastase inhibitors like alpha-1-antitrypsin, leading to fiber fragmentation [2,14-19].
Abnormal elastic fiber production
Abnormalities in elastic fiber production and copper metabolism further contribute, affecting the structural integrity of the skin elastic fiber production [2,14,20-22].
Inflammation induced elastolysis
Inflammation activates enzymes like matrix metalloproteinases contributing to the breakdown of elastic fibers [2,23,24]. In addition, chronic inflammatory conditions play roles in elastic fiber breakdown, via release of many cytokines and neutrophil recruitment, alongside potential genetic predispositions that influence susceptibility [2,25,26].
Malignancy induced immune-complexes
Immunoglobulins, particularly IgG and IgA, can lead to elastolysis by either directly damaging elastic fibers or activating complement pathways through binding to macrophages and neutrophils. This process results in the formation of immune complexes, which may subsequently lead to the destruction of elastic fibers via phagocytosis or alternative complement pathway activation [2,26,27]. Histologically, IgG or IgA immunoglobulins have been observed around fragmented elastic fibers in cases associated with specific gammopathies, supporting this mechanism [11,13,27-32].
Diagnostic Evaluation
The diagnostic evaluation for ACL involves a thorough assessment (Summarized in Figure 1) to determine the underlying cause and evaluate the extent of skin and systemic involvement. Dermatologists play a crucial role in gathering information about associated symptoms, and relevant medical history such as autoimmune diseases, inflammatory conditions, recent infections, or drug use. Laboratory investigations may include tests like complete blood count, inflammatory markers, autoimmune serology, and specific serum tests for elastase, alpha-1-antitrypsin, copper, and ceruloplasmin levels. Skin biopsies are essential for examining the elastic fibers. Imaging studies such as echocardiography, pulmonary function tests, and abdominal scans may be used to assess internal organ involvement, particularly in cases of widespread ACL with systemic symptoms [2]. Hematologists or oncologists should be consulted if there is suspicion of a gammopathy or a malignancy, requiring tests like beta-2 microglobulin, serum lactate dehydrogenase, serum and urine protein electrophoresis, and potentially a bone marrow biopsy. Regular follow-up is recommended, focusing on monitoring for monoclonal proteins to detect any potential progression of underlying neoplasm, which can sometimes develop years after the onset of ACL [2,8,27,28,33,34].
Treatment and Outcomes
The treatment of ACL is primarily surgical, focusing on the removal of excess lax skin. However, controlling the underlying disease is crucial to stop the progression and prevent recurrence post-surgery [31,35-41]. Treatment should be tailored to the specific underlying cause. For non-neoplastic ACL cases such as urticaria or neutrophilic dermatosis associated ACL dapsone is the drug of choice, given at a dose of 50 to 100 mg daily with major improvement in the underlying conditions and skin laxity progression [16,19,35,42]. Systemic steroids and adalimumab stopped disease advancement in cases secondary to sweet syndrome [10,43-45]. For extensive generalized cases and those with systemic involvement, prompt immunosuppressive therapy is recommended [2]. In idiopathic cases with secondary renal involvement, such as those documented by Peralta-Amaro et al. and Tsuji et al., where no underlying disease was identified, the introduction of systemic immunosuppressants (including systemic steroids, cyclophosphamide, rituximab, and mycophenolate mofetil) appeared effective. These treatments not only halted the progression of the cutaneous symptoms but also led to improvements in renal function tests [14,55]. For neoplastic associated cases, when an underlying gammopathy is confirmed, referral to a hematologist for appropriate chemotherapy or immunomodulatory treatment is preferred. Agents used include systemic steroids, methotrexate [13], hydroxychloroquine [13], lenalidomide [46], bortezomib [27,32,33,47-49], danazol [47], cyclophosphamide [50-52], vincristine, doxorubicin, melphalan [51], bendamustine/rituximab [52,53], intravenous immunoglobulin [47] and autologous peripheral stem cell or bone marrow transplantation [48,49]. These treatments regimens and their outcome are summarized in Table 2. Among the reported cases, 16 with an underlying neoplasm were treated with chemotherapy. In 9 cases (60%), no progression in skin laxity was observed after initiating chemotherapy [14,32,33,47-50,53,54]. However, 6 cases reported no improvement [13,27,28,46,51,52], with worsening cutaneous outcomes, and for the recent case by Zhang et al., no outcome data post-treatment with antiplasma cell therapy is available [4].
Conclusion
ACL presents a complex dermatological challenge linked increasingly to hematological disorders, particularly monoclonal gammopathies. Recent advancements underscore its role as a potential paraneoplastic marker, highlighting the need for vigilant hematological evaluation and long-term patient follow-up in clinical practice. Continued research into pathogenesis and therapeutic strategies is crucial for enhancing outcomes and refining clinical guidelines in ACL management. Effective management of ACL requires interdisciplinary collaboration among dermatologists, hematologists, cardiologists, gastroenterologists, pulmonologists, and other specialists to ensure comprehensive care. Continued research into the pathogenesis and therapeutic strategies of ACL is crucial for enhancing patient outcomes and refining clinical guidelines in its management.
Conflict of Interest
None.
Data Availability
The data used to support the findings of this study are included within the article.
Ethics Statement
This study was not performed on any human or animal subjects and no informed consent was needed.
Author Contributions Statement
Both authors contributed equally in drafting this commentary.
References
2. Khodeir J, Ohanian P, Feghali J. Acquired cutis laxa: a clinical review. Int J Dermatol. 2024 Jun 25.
3. Claveau JS, Wetter DA, Kumar S. Cutaneous manifestations of monoclonal gammopathy. Blood Cancer J. 2022 Apr 11;12(4):58.
4. Zhang L, Jin L, Zhao Y, Cai H, Gu W. A case of monoclonal gammopathy of cutaneous significance with multiple organs involvement: Comment on "Concurrent acquired cutis laxa and necrobiotic xanthogranuloma without paraproteinemia". J Dermatol. 2024 Apr 17.
5. Verhagen AR, Woerdeman MJ. Post-inflammatory elastolysis and cutis laxa. Br J Dermatol. 1975 Feb;92(2):183-90.
6. Reed WB, Horowitz RE, Beighton P. Acquired cutis laxa: primary generalized elastolysis. Archives of Dermatology. 1971 Jun 1;103(6):661-9.
7. Kerl H, Burg G, Hashimoto K. Fatal, penicillin-induced, generalized, postinflammatory elastolysis (cutis laxa). The American Journal of Dermatopathology. 1983 Jun 1;5(3):267-76.
8. Turner RB, Haynes HA, Granter SR, Miller DM. Acquired cutis laxa following urticarial vasculitis associated with IgA myeloma. Journal of the American Academy of Dermatology. 2009 Jun 1;60(6):1052-7.
9. Gonzalez‐Ramos J, Garrido‐Gutiérrez C, González‐Silva Y, Yébenes‐Gregorio L, Beato‐Merino M, Vidaurrázaga‐Arcaya C, et al. Relapsing bullous amyloidosis of the oral mucosa and acquired cutis laxa in a patient with multiple myeloma: a rare triple association. Clinical and Experimental Dermatology. 2017 Jun 1;42(4):410-2.
10. Hwang ST, Williams ML, McCalmont TH, Frieden IJ. Sweet's Syndrome Leading to Acquired Cutis Laxa (Marshall's Syndrome) in an Infant With a1-Antitrypsin Deficiency. Archives of Ermatology. 1995 Oct 1;131(10):1175-7.
11. Cho SY, Maguire RF. Multiple myeloma associated with acquired cutis laxa. Cutis. 1980 Aug 1;26(2):209-11.
12. Appiah YE, Onumah N, Wu H, Elenitsas R, James W. Multiple myeloma–associated amyloidosis and acral localized acquired cutis laxa. Journal of the American Academy of Dermatology. 2008 Feb 1;58(2):S32-3.
13. Kluger N, Molès JP, Vanakker OM, Pernet C, Beylot-Barry M, Bessis D. Acral acquired cutis laxa associated with IgA multiple myeloma, joint hyperlaxity and urticarial neutrophilic dermatosis. Acta Dermato-Venereologica. 2014 Apr 8;94(6):743-4.
14. Peralta-Amaro AL, Quintal-Ramírez MJ, Esteban-Prado A, Chávez-Sánchez IN, Vera-Lastra OL, López-Velasco A, et al. Type I acquired cutis laxa: Report of a unique progressive case and short review. Am J Med Sci. 2024 Apr;367(4):268-273.
15. Takenaka Y, Ishiguro N, Kawashima M. Case of acquired cutis laxa with preceding urticarial eruption treated by diphenyl sulfone. J Dermatol. 2018 Nov;45(11):e292-e293.
16. Bostan E, Yalici-Armagan B, Gokoz O. Chronic urticaria may not be as innocent as we think: A rare case of acquired cutis laxa following chronic urticaria. J Cosmet Dermatol. 2022 Jul;21(7):3154-6.
17. Katsuren K, Kuba R, Kasai S, Shimizu Y. Acquired Cutis Laxa on the Upper Eyelids and Earlobes: A Case Report and Literature Review. Arch Plast Surg. 2022 May 27;49(3):418-22.
18. Nygaard RH, Maynard S, Schjerling P, Kjaer M, Qvortrup K, Bohr VA, et al. Acquired Localized Cutis Laxa due to Increased Elastin Turnover. Case Rep Dermatol. 2016 Feb 13;8(1):42-51.
19. Fauconneau A, Sokolowsky N, Camus M, Darrigade AS, Guillet S, Jullie ML, et al. Acquired cutis laxa associated with neutrophilic urticarial dermatosis. Int J Dermatol. 2021 Jun;60(6):771-2.
20. Na SY, Choi M, Kim MJ, Lee JH, Cho S. Penicillamine-induced Elastosis Perforans Serpiginosa and Cutis Laxa in a Patient with Wilson's Disease. Ann Dermatol. 2010 Nov;22(4):468-71.
21. Mehta B, Amladi S. Acquired localized cutis laxa of the face: a rare presentation. Pediatr Dermatol. 2011 Jul-Aug;28(4):421-3.
22. Lewis BK, Chern PL, Stone MS. Penicillamine-induced elastosis of the mucosal lip. J Am Acad Dermatol. 2009 Apr;60(4):700-3.
23. Gu W, Liu W, Yang X, Yuan X, Tian Y, Meng R, et al. Cutis laxa: analysis of metalloproteinases and extracellular matrix expression by immunohistochemistry and histochemistry. Eur J Dermatol. 2011 Sep-Oct;21(5):717-21.
24. Yamamoto T, Hasegawa T, Nakano H. Acquired localized cutis laxa occurring on the face after delivery. Eur J Dermatol. 2015 May-Jun;25(3):266-7.
25. Hu Q, Reymond JL, Pinel N, Zabot MT, 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. 2006 Feb;126(2):283-90.
26. Nikko A, Dunnigan M, Black A, Cockerell CJ. Acquired cutis laxa associated with a plasma cell dyscrasia. Am J Dermatopathol. 1996 Oct;18(5):533-7.
27. Gonzalez-Rodriguez AJ, Bella-Navarro R, Ramon Quiles D, Jorda-Cuevas E. Cutis laxa adquirido asociado a gammapatía monoclonal y enfermedad por depósito de cadenas ligeras lambda. Dermatology Online Journal. 2014;20(5).
28. Shalhout SZ, Nahas MR, Drews RE, Miller DM. Generalized Acquired Cutis Laxa Associated with Monoclonal Gammopathy of Dermatological Significance. Case Rep Dermatol Med. 2020 Feb 12;2020:7480607.
29. García‐Patos V, Pujol RM, Barnadas MA, Pérez M, Moreno A, Condomines J, et al. Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres. British Journal of Dermatology. 1996 Jul;135(1):130-4.
30. Maruani A, Arbeille B, Machet MC, Barbet C, Laure B, Martin L, et al. Ultrastructural demonstration of a relationship between acquired cutis laxa and monoclonal gammopathy. Acta Derm Venereol. 2010 Jul;90(4):406-8.
31. Tan S, Pon K, Bargman J, Ghazarian D. Generalized cutis laxa associated with heavy chain deposition disease. J Cutan Med Surg. 2003 Sep-Oct;7(5):390-4.
32. Bennassar A, Mascaro JM, Julia M. Generalized acquired cutis laxa associated with immunoglobulin G-lambda monoclonal gammapathy. J Am Acad Dermatol. 2009;60(3):AB65.
33. Fernández de Larrea C, Rovira M, Mascaró JM Jr, Torras A, Solé M, Lloreta J, et al. Generalized cutis laxa and fibrillar glomerulopathy resulting from IgG Deposition in IgG-lambda Monoclonal Gammopathy: pulmonary hemorrhage during stem cell mobilization and complete hematological response with bortezomib and dexamethasone therapy. Eur J Haematol. 2009 Feb;82(2):154-8.
34. Xue Y, Chen H, Zeng X, Jiang Y, Sun J. Generalized acquired cutis laxa treated with facial plastic surgery. Eur J Dermatol. 2011 Jan-Feb;21(1):141-2.
35. Riveros CJ, Gavilán MF, França LF, Sotto MN, Takahashi MD. Acquired localized cutis laxa confined to the face: case report and review of the literature. Int J Dermatol. 2004 Dec;43(12):931-5.
36. Mitra S, Agarwal AA, Das JK, Gangopadhyay A. Cutis laxa: a report of two interesting cases. Indian J Dermatol. 2013 Jul;58(4):328.
37. Yadav TA, Dongre AM, Khopkar US. Acquired cutis laxa of face with multiple myeloma. Indian J Dermatol Venereol Leprol. 2014 Sep-Oct;80(5):454-6.
38. Law MX, Kersten C, Kalin-Hajdu E. Acquired Cutis Laxa Presenting as Pedunculated Eyelid Plaques in an Adult. Ophthalmology. 2018 Dec;125(12):1952.
39. Yamashita A, Fukui T, Akasaka E, Nakajima K, Nakano H, Sawamura D, et al. Acquired cutis laxa secondary to acute generalized exanthematous pustulosis: A case report and mini-review of literature. J Dermatol. 2024 Feb;51(2):287-293.
40. Reddy GP, Mishra B, Upadhyaya DN. Acquired Localized Cutis Laxa: A Case Report and the Role of Plastic Surgery. Indian J Dermatol. 2019 Jan-Feb;64(1):55-58.
41. Paulsen IF, Bredgaard R, Hesse B, Steiniche T, Henriksen TF. Acquired cutis laxa: diagnostic and therapeutic considerations. J Plast Reconstr Aesthet Surg. 2014 Oct;67(10):e242-3.
42. Fisher BK, Page E, Hanna W. Acral localized acquired cutis laxa. J Am Acad Dermatol. 1989 Jul;21(1):33-40.
43. Rosier P, Deroux A, Beyens A, Callewaert B, Leccia MT. Major response to adalimumab in patient with Sweet syndrome associated to an acquired cutis laxa. J Eur Acad Dermatol Venereol. 2022 May;36(5):e354-e356.
44. Jagati A, Shrivastava S, Baghela B, Agarwal P, Saikia S. Acquired cutis laxa secondary to Sweet syndrome in a child (Marshall syndrome): A rare case report. J Cutan Pathol. 2020 Feb;47(2):146-9.
45. Timmer-DE Mik L, Broekhuijsen-VAN Henten DM, Oldhoff JM, DE Geer DB, Sigurdsson V, Pasmans SG. Acquired cutis laxa in childhood Sweet's syndrome. Pediatr Dermatol. 2009 May-Jun;26(3):358-60.
46. New HD, Callen JP. Generalized acquired cutis laxa associated with multiple myeloma with biphenotypic IgG-λ and IgA-κ gammopathy following treatment of a nodal plasmacytoma. Arch Dermatol. 2011 Mar;147(3):323-8.
47. Kim DP, Klein PA. Acquired cutis laxa in a 55-year-old female with multiple myeloma and serologic evidence of systemic lupus erythematosus. Dermatology online Journal. 2011 Jul 1;17(7):8.
48. Lee MY, Byun JY, Choi YW, Choi HY. Multiple myeloma presenting with acquired cutis laxa and primary systemic amyloidosis. Eur J Dermatol. 2017 Dec 1;27(6):654-5.
49. Lavorato FG, Alves Mde F, Maceira JM, Unterstell N, Serpa LA, Azulay-Abulafia L. Primary systemic amyloidosis, acquired cutis laxa and cutaneous mucinosis in a patient with multiple myeloma. An Bras Dermatol. 2013 Nov-Dec;88(6 Suppl 1):32-5.
50. Majithia RA, George L, Thomas M, Fouzia NA. Acquired Cutis Laxa Associated with Light and Heavy Chain Deposition Disease. Indian Dermatol Online J. 2018 Jan-Feb;9(1):44-46.
51. Gupta A, Helm TN. Acquired cutis laxa associated with multiple myeloma. Cutis. 2002 Feb;69(2):114-8.
52. Galiczynski. Acquired cutis laxa associated with monoclonal gammopathy. J Am Acad Dermatol. 2009;60(3):AB45.
53. Lim DJ, Yang HJ, Lee MY, Lee WJ, Won CH, Chang SE, et al. A rare case of secondary cutaneous lymphoplasmacytic lymphoma clinically presenting as acquired cutis laxa. J Cutan Pathol. 2024 Feb;51(2):135-9.
54. Dicker TJ, Morton J, Williamson RM, Chick J. Myeloma-associated systemic amyloidosis presenting with acquired digital cutis laxa-like changes. Australas J Dermatol. 2002 May;43(2):144-6.
55. Tsuji T, Imajo Y, Sawabe M, Kuniyuki S, Ishii M, Hamada T, Ishimura E, Hamada N, Nishisawa Y, Morii H. Acquired cutis laxa concomitant with nephrotic syndrome. Arch Dermatol. 1987 Sep;123(9):1211-6.
56. Jain A. Acquired Cutis Laxa. Turk J Haematol. 2020 Aug 28;37(3):212-3.
57. Silveira L, Torres I, Salvino MA, Follador I, Bittencourt AL. Acquired cutis laxa with an interstitial granulomatous reaction associated with IgG lambda monoclonal gammopathy. Am J Dermatopathol. 2013 Jun;35(4):e67-71.
58. Ferrándiz-Pulido C, Serra M, Bel S, Ferrer B, Repiso T, Garcia-Patos V. Multiple myeloma-associated amyloidosis presenting with acrolocalized acquired cutis laxa. Arch Dermatol. 2010 Dec;146(12):1433-4.
59. Moretta G, Moro F, Fania L, Didona B. Generalized acquired cutis laxa and urticarial dermatosis associated with k-chain IgA micromolecular myeloma. Dermatol Reports. 2021 Aug 5;13(2):9146.
60. O'Connell KA, Schaefer M, Atzmony L, Vleugels RA, Choate K, LaChance AH, Min MS. Clinical features in adults with acquired cutis laxa: a retrospective review. Br J Dermatol. 2023 May 24;188(6):800-16.
61. Chartier S, Faucher L, Tousignant J, Rochette L. Acquired cutis laxa associated with cutaneous angiocentric T-cell lymphoma. Int J Dermatol. 1997 Oct;36(10):772-6.
62. Hinck A, Hinek A, Dutz J, Martinka M. A novel defect in fibrillin-1 deposition by dermal fibroblasts clinically presenting as acquired cutis laxa is reversible with dexamethasone and losartan treatment. J Am Acad Dermatol. 2011;64(2):AB53.
63. New D, Callen J. Acquired cutis laxa and granuloma annulare-like lesions secondary to multiple myeloma. J Am Acad Dermatol. 2010;62(3):AB43.
64. Van Meurs T. Acquired cutis laxa: Associated with a monoclonal gammopathy of unknown significance (MGUS)? Ned Tijdschr Voor Dermatol En Venereol. 2006 Oct 31;2006:242-4.