Acquired Cutis Laxa Secondary to Hematological Malignancy: A Report of Two Cases

Dear Editor, Cutis laxa (CL) is a rare connective tissue disorder characterized by loose, saggy skin that gives a prematurely aged appearance and can be inherited (childhood-onset) or acquired (adult-onset).[1-3] Herein, we report two cases of acquired CL (ACL) with underlying hematological malignancies, emphasizing its potential role as a paraneoplastic marker. Case 1: A 35-year-old male presented with a two-year history of loose, wrinkled skin, which started on the face, neck, and progressively involved the axillae and groins. His medical and family history were noncontributory. Systemic examination was normal, and cutaneous examination revealed loose, pendulous, wrinkled skin with delayed recoil on the face, neck, axillae, and groins, with minimal periorbital edema [Figure 1].Figure 1: (a) Pendulous and wrinkled skin on the face; (b) neck; (c) axillae; (d) groins; (e) histopathology showing dermal collagenisation with mild perivascular chronic inflammation (hematoxylin and eosin, original magnification, 100×); (f) reduced elastic fibers in the reticular dermis (orcein, original magnification, 100×)Skin biopsy from the neck and axillae, on hematoxylin and eosin (H and E) and orcein stain, showed reduced elastic fibers in the reticular dermis, confirming CL [Figure 1]. He had low serum complements; serum electrophoresis revealed M band in the gamma region, and elevated IgG-lambda chain on immunofixation electrophoresis (IFE). Bone marrow biopsy with immunohistochemistry (CD138) showed hypercellular marrow with mild plasmacytosis (~10%) and lambda light-chain restriction, consistent with plasma cell dyscrasia. A diagnosis of generalized ACL with hypocomplementemia secondary to plasma cell dyscrasia was made. The hematologist initiated CyBorD protocol (cyclophosphamide, bortezomib, dexamethasone), which normalized serum-free light-chain ratio and arrested progression. Surgical correction of the redundant skin folds was advised. Case 2: A 58-year-old man with hypothyroidism presented with facial and periorbital sagging of one-year duration. Examination revealed blepharochalasia, facial sagging, bilateral cervical, axillary, and inguinal lymphadenopathy. Skin biopsy from the infraorbital region showed decreased elastic fibers suggestive of CL [Figure 2]. Evaluation revealed elevated free kappa-chain levels, increased kappa/lambda ratio, and immunoglobulin G kappa on IFE. Lymph node and bone marrow biopsy with immunohistochemistry showed atypical lymphocytes favoring marginal zone lymphoma. He was diagnosed with ACL secondary to kappa-chain deposition due to marginal zone lymphoma and was referred to hematology, but lost to follow-up.Figure 2: (a) Blepharochalasia and facial sagging; (b) dermal collagenisation with mild perivascular chronic inflammation (hematoxylin and eosin, original magnification, 100×); (c) reduced elastic fibers in the reticular dermis (orcein, original magnification, 100×)ACL has two types. Type-I ACL, as seen in our cases, is typically adult-onset, insidious, localized/generalized, progressing cephalocaudally and is often associated with inflammatory dermatoses, malignancies, infections, or drugs. It may involve multiple organ systems, which increases mortality.[1,4] Type-II ACL (Marshall syndrome) is a post-inflammatory elastolysis, usually affecting children, with laxity limited to prior inflammation sites and occasional cardiac involvement.[2] Khodeir et al. reviewed 110 ACL patients (mean age: 36.4 years, slight male predominance, male to female ratio-1.24). Associations included inflammatory disorders (43%), paraneoplastic disorders (27%), medications (10%), infections (2%), and miscellaneous/idiopathic cases (18%).[1] All 30 paraneoplastic cases had underlying hematological malignancies: multiple myeloma (n=15), monoclonal gammopathy of undetermined significance (MGUS, n=6), monoclonal gammopathy of renal significance (MGRS, n=6), lymphomas (n=2), and unspecified plasma cell dyscrasias (n=1). ACL preceded malignancies by an average of 2.4 years, with predominantly generalized ACL (83%) and isolated acral involvement observed in only 17% cases. Our cases closely mirror these findings. ACL pathogenesis is multifactorial, including immune-mediated elastolysis, enzymatic degradation (increased elastase activity, reduced elastase inhibitors like alpha-1 antitrypsin), inflammation-induced elastolysis by matrix metalloproteinases, abnormal elastic fiber production, and immunoglobulin-mediated destruction. Paraproteins, particularly IgG and IgA, can induce elastolysis through direct damage or complement activation.[1] Hypocomplementemia in Case 1 supports an immune complex-mediated mechanism, whereas light-chain excess in Case 2 suggests paraprotein-related elastic fiber damage, highlighting the pathogenetic heterogeneity. Recognizing clinical patterns in ACL aids evaluation.[1,2] Malignancy-associated ACL is insidious, generalized, and may progress cephalocaudally, with clues like older age, weight loss, anemia, renal dysfunction, lymphadenopathy, and bone pain. Drug-associated ACL correlates temporally with the medication. Inflammatory causes are generalized with specific features: systemic lupus erythematosus (photosensitivity, oral ulcers, arthritis), sarcoidosis (pulmonary symptoms, lymphadenopathy), and amyloidosis (neuropathy, purpura, macroglossia, renal involvement). Infection-associated ACL may follow a prodrome, with exposures suggesting borrelia (tick/endemic travel), syphilis (high-risk behavior/genital ulcers), or toxocara (zoonotic/soil exposure with eosinophilia). Comprehensive evaluation includes detailed history (drug intake, recent infections, prior autoimmune/inflammatory disorders), physical examination, and tailored laboratory tests including serum electrophoresis [Table 1]. Histopathology shows reduced elastic fibers with fragmentation, shortening, degeneration, or a bramble-bush appearance. Special stains (Verhoeff–van–Gieson or orcein) highlight these findings.[1,2] Relevant imaging studies are required for suspected systemic involvement. As ACL often precedes malignancy, regular follow-up is crucial.Table 1: Overview of the evaluation of a patient with acquired cutis laxaWhile skin laxity is often irreversible, early identification and treatment of the underlying cause are crucial. Non-neoplastic causes, such as urticaria or neutrophilic dermatoses, may respond to dapsone, whereas inflammatory etiologies require appropriate immunosuppressive therapy. Neoplastic causes necessitate hemato-oncologist referral for chemotherapy or immunomodulatory treatment. Adjunctive options include retinoids, fractional CO2 laser, energy-based devices, and botulinum toxin. Surgical correction (rhytidectomy, blepharoplasty) is considered after disease quiescence.[3,4] ACL warrants detailed evaluation. Given its potential to precede neoplastic disorders, particularly hematological malignancies, ACL should prompt a vigilant hematological workup and long-term follow-up. Authors’ contributions All authors have approved the manuscript and are accountable for its content. All authors meet authorship criteria and the manuscript represents our honest work. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The preparation of this manuscript was carried out entirely by the authors without the use of artificial intelligence technologies.