Generalized Acquired Cutis Laxa Associated with Monoclonal Gammopathy of Dermatological Significance

Table 1

Summary of acquired cutis laxa associated with monoclonal gammopathies/plasma-cell dyscrasia.

Reference	Sex, age	Preceding cutaneous eruptions	Clinical features	Associated plasma-cell dyscrasia/monoclonal gammopathy	Treatment	Outcome
Scott et al. [5]	F, 44	Edema of face and neck from hypersensitivity reaction to penicillin	Skin laxity to face and neck, followed by progression to extremities and torso; systemic involvement (gastrointestinal and urogenital)	Multiple myeloma	Surgical repair of hernias/prolapses	Not reported
Ting et al. [6]	F, 45	Intermittent “puffiness” of eyelids	Progressive laxity of the skin starting from the eyelids and spreading gradually to the face, neck, trunk, lungs, rectum, bladder, and perineum	Multiple myeloma	Not reported	Not reported
Frémont et al. [7]	F, 59	None reported	Skin hyperlaxity present for several years	IgG lambda myeloma	Thalidomide	One year after treatment, skin laxity stabilized
Gupta and Helm [8]	F, 62	Denied any prior inflammatory skin disorder or exanthema	Progressive laxity to face, neck, chest, and back; no rectal or vaginal prolapse, emphysema, or cardiac problems detected	Multiple myeloma	Prior to CL onset, patient received vincristine, melphalan, doxorubicin, cyclophosphamide, and prednisone with improvement to hematological disease	Patient was on prednisone during onset of CL; thalidomide gradually increased; but no improvement to cutis laxa was observed
Turner et al. [9]	M, 29	2-year history of asymptomatic urticarial red papules and plaques on the neck, chest, and back lasting days at a time, urticarial vasculitis	Wrinkling and sagging skin on the face, neck, axillae, shoulders, and arms with transverse striae on abdomen, leukocytoclastic vasculitis, and immune complex-mediated glomerulonephritis	IgA myeloma involving kidneys	High-dose methyl prednisolone, and intravenous cyclophosphamide	Initially, all urticarial skin lesions resolved; eventually, renal function deteriorated, and the patient became dependent on dialysis; patient eventually succumbed to his disease
Kluger et al. [10]	M, 40	Chronic urticarial dermatosis of the extremities, mostly involving the hands, progressively worsened, with repeated swelling of the fingers	Acral localization of cutis laxa, joint hyperlaxity, and recurrent neutrophilic urticarial dermatosis	IgA multiple myeloma	Methotrexate, colchicine, hydroxychloroquine, intravenous gamma globulins, and dapsone, oral prednisone	Treatment with oral prednisone resulted in complete remission of the urticarial lesions, with steroid dependence; prevention of the progression in joint laxity or cutis laxa was not achieved
Lavorato et al. [11]	F, 57	Bilateral eyelid hyperchromia, and increase in palpebral volume	Cutaneous laxity in skin folds, bilateral palpebral ptosis, pain and paresthesia, histological and clinical features consistent with primary systemic amyloidosis, cutaneous mucinosis, and acquired cutis laxa	Multiple myeloma associated amyloidosis	Bortezomib and dexamethasone, followed by autologous bone marrow transplantation	“Clinically important dermatological improvement” was achieved
Yoneda et al. [12]	M, 62	None reported, but presented with lumbago and shoulder pain, with a history of severe fatigue and night sweats	Soft, redundant, cutaneous laxity to acral sites on fingertips and soles of feet, lumbago	Myeloma associated amyloidosis	Cyclophosphamide and prednisolone	Treatment decreased hematological disease but the cutis laxa of acral sites progressed; patient eventually succumbed to his disease
Yoneda et al. [12]	M, 71	None reported, but presented with lumbar and back pain, with a history of leg pain, weakness, and night sweats	Soft, loose skin changes to both thumbs	Myeloma associated amyloidosis	Cyclophosphamide	Chemotherapy resulted in a decrease of hematological disease, but cutaneous lesions did not regress; continued follow-up at time of report
Nikko et al. [3]	F, 40	Denied any prior inflammatory skin disorder	Progressive wrinkling, and laxity of the skin on back, chest, abdomen, upper arms, neck, thighs but face was spared	Plasma-cell dyscrasia	None reported	Careful follow-up in case of systemic complication at the time of report.
Lee et al. [13]	F, 54	One-year previous history of easy bruising	Hypopigmented patches with skin laxity, purpura on both flanks, periorbital purpura, lax skin of thumbs; histological, and clinical features consistent with acquired cutis laxa, and primary systemic amyloidosis	Multiple myeloma associated amyloidosis	Bortezomib, thalidomide, dexamethasone followed by autologous peripheral blood stem cell transplant	Slight clinical improvement of skin was noted
Dicker et al. [14]	F, 59	“Puffiness” in fingertips, tender with pressure, tense before resolving to lax skin	Persistent laxity of skin on finger pads, and tongue swelling	Plasma cell dyscrasia	Cyclophosphamide, vincristine, adriamycin, and methylprednisolone	Reduction in size of tongue and a decrease in laxity of skin lesions were achieved
Appiah et al. [15]	F, 64	History of multiple asymptomatic skin lesions in groin and axillae	Flesh-colored papules in axillae and groin, papules with purpura on eyelids, translucent papules and nodules on labia majora, wrinkled loose skin on fingertips	Myeloma associated amyloidosis	Not reported	Not reported
Ferrandiz-Pulido et al. [16]	M, 63	3-month history of asymptomatic skin lesions on ventral aspect of fingers	Soft redundant loose skin on all fingertips and hands	Multiple myeloma-associated amyloidosis	Not reported	Not reported
Silveira et al. [17]	M, 29	Diffuse erythematous plaques, mildly infiltrated papules, and plaques on his trunk	Multiple flaccid erythematous plaques on trunk, neck, and skinfolds with flaccidity of face, axillae, groin, neck, hiatal hernia, eventually developed nephrotic syndrome and acute renal failure	IgG lambda monoclonal gammopathy	Bortezomib, dexamethasone, and thalidomide	No improvement to dermatological lesions observed
New and Callen [4]	M, 48	No preceding cutaneous changes, but he developed erythematous plaques and granuloma annulare like features on his buttocks and lateral hips	4-year history of loose wrinkled skin of his face, chest, upper back, lateral hips, buttocks, and proximal upper extremities	Multiple myeloma	Lenalidomide, dexamethasone, oral pamidronate, and aspirin	With 5 months of therapy, patient had hematological and skeletal lesion stabilization, but his cutis laxa progressed during treatment.
Gonzalez-Ramos et al. [18]	M, 68	3-month history of stable asymptomatic multiple myeloma (progressed after 5 years with MGUS) and 2-month history of hemorrhagic bullae in oral buccal and labial mucosa before presentation	Numerous large hemorrhagic oral bullae, yellowish and purple purpura plaques on eyelids and macroglossia, cutis laxa of axilla and antecubital flexure; clinical and histological features consistent with primary systemic amyloidosis and acquire cutis laxa	Multiple myeloma associated amyloidosis	Intensive chemotherapy	No recurrence of skin lesions; at the time of the report, the patient was awaiting an autologous bone marrow transplant
Tan et al. [19]	M, 50	No preceding skin lesions, and his skin was otherwise asymptomatic, a history of heavy chain deposition disease without evidence of multiple myeloma preceding any cutaneous findings	Weight loss and significant lax skin of axillae, groin, neck, face with periocular involvement with upper lid ptosis and lower lid laxity; subsequent emphysema, leg weakness and peripheral polyneuropathy; no known herniations, diverticula, or aneurysms	Heavy chain deposition disease/monoclonal gammopathy	Prednisone and cyclophosphamide but he presented to dermatological service with end-stage disease, medical therapy for the skin condition was not attempted	There was a transient improvement in renal function; the patient underwent functional blepharoplasty to relieve the ectropion/epiphora
O’Malley et al. [20]	F, 60–69	No preceding cutaneous eruptions; a history of nephrotic syndrome and renal insufficiency due to renal heavy chain deposition disease	Extensive emphysema, lower extremity edema with relapse of her heavy chain deposition disease, marked “hound-dog” facies with lax skin encompassing face, neck, and arms; onset correlating with the time renal involvement was first diagnosed	Heavy chain deposition disease/low-grade plasma-cell neoplasm (complement components on dermal elastic fibers also detected)	Bortezomib and pulse dexamethasone	The patient had subsequent improvement of her nephrotic syndrome and resolution of her acute kidney injury; cutaneous outcome not discussed.
Harrington et al. [21]	F, 38	A history of urticaria, renal insufficiency, heavy chain deposition in heart and kidneys, bilateral lower extremity edema	Excessive wrinkling of the skin that began in the axillae a few years before presentation and progressed to involve her face, extremities, and trunk	Heavy chain deposition disease/monoclonal gammopathy	Lenalidomide with progression of renal failure, requiring temporary dialysis and the discontinuation of this medication; stabilized on bortezomib and dexamethasone	The cutaneous outcome was not described
de Larrea et al. [22]	M, 52	None reported	Cutis laxa of the face, neck, axillae, and groin in the setting of MGUS, renal failure	IgG lambda monoclonal gammopathy	Initially, he was treated with granulocyte CSF but developed alveolar hemorrhage and decreased renal function; he was later treated with bortezomib and oral dexamethasone	A complete hematological response without an increase in bone marrow plasma cells was achieved; he was still on chronic hemodialysis at time of report but his cutis laxa had not progressed, and the patient planned for surgical correction of redundant skin folds.
Majithia et al. [23]	M, 40	None reported; but gave a history of fatigue, shortness of breath, and edema	Loose hanging ear lobes, blepharochalasis, lax nasolabial folds, and increased folds over the neck, axilla, and trunk progressing over two years.	Light and heavy chain deposition disease (LHCDD)	Dexamethasone, cyclophosphamide, and bortezomib	Patient had significant improvement clinically and with hematological disease but was lost to follow-up.
Kim and Klein [24]		She had no history of an inflammatory preceding cutaneous process.	Patient presented with a 10-year history of lax skin with progression in recent years to face, neck, and legs; she was diagnosed with MGUS and eventually light chain multiple myeloma, anemia, and immune-mediated glomerular nephritis; in aggregate, findings were consistent with acquired cutis laxa and systemic lupus erythematosus associated with multiple myeloma	Multiple myeloma and systemic lupus erythematosus	Lenalidomide and low-dose dexamethasone for multiple myeloma. Later, she was treated with bortezomib and dexamethasone, followed by IVIG and danazol	She had a good response to lenalidomide and dexamethasone in terms of reduction of light chain disease, but therapy was discontinued due to cytopenia; excellent response to bortezomib and dexamethasone but discontinued therapy due to cytopenia; IVIG and danazol stabilized her blood counts.
Current case	M, 35	None reported	Profound laxity of the periocular skin, neck, axillary and back which progressed over the period of one year; aortitis, several hernias and diverticula.	Multiple myeloma	Cyclophosphamide, bortezomib, dexamethasone, (CyBorD) herniorrhaphy, and high-dose prednisone	His hematological disease stabilized on CyBorD, and high-dose prednisone improved vasculitis; his cutis laxa has not progressed one-year posttreatment.