Acquired cutis laxa in a 55-year-old female with multiple myeloma and serologic evidence of systemic lupus erythematosus

Cutis laxa (CL) is a rare connective tissue disorder characterized by loosely hanging skin folds. Histopathology reveals degenerative changes in the dermal elastic fibers, although loss of elastin can also occur in alveolar walls, blood vessels, and other organs. The coexistence of autoimmune diseases and monoclonal gammopathies is rare but well documented in the literature. Here we report an unusual case of cutis laxa (CL) preceding the development of serologic evidence of systemic lupus erythematosus (SLE) and a diagnosis of multiple myeloma (MM) by seven and eleven years respectively.     

Acquired cutis laxa and myeloma: large vacuolated cells in the dermis

INTRODUCTION: Cutis laxa is a rare disorder characterized by loss of elastic tissue. Several organs are often involved such as the skin, lungs, heart, digestive system or genitourinary tract. It may be inherited or acquired, generalized or localized. Its pathogenesis is unclear. Association of acquired cutis laxa with myeloma or plasma cell dyscrasia is very rare. We report a case of acquired cutis laxa associated with a myeloma. CASE REPORT: A 59 year-old woman was admitted for skin hyperlaxity present for a number of years. Light microscopic examination of a skin sample revealed fragmented elastic fibers. Electron microscopic examination of the elastic network demonstrated numerous large vacuolated cells with the appearance of macrophages around abnormal elastic and collagen fibers of the reticular dermis. In addition, a stage-1 IgG lambda myeloma was detected. The patient was treated by thalidomide for one year. After this treatment, electron microscopy examination did not reveal any large vacuolated cells in the dermis, and elastic and collagen fibers were not modified and skin laxity seemed to be stabilized. DISCUSSION: Acquired cutis laxa may be associated with many systemic diseases or can appear after inflammatory skin diseases. Seven cases of generalized cutis laxa associated with myeloma and four cases associated with plasma cell dyscrasia have been reported in the literature. In our case, as in 2 previously described cases, large vacuolated cells resembling macrophages were seen in the dermis. They were thought to play a role in cutis laxa.     

Acral localized acquired cutis laxa as presenting sign of underlying systemic amyloidosis

Acral localized acquired cutis laxa (ALACL) is a rare variant of acquired cutis laxa, and the clinical appearance is characterized by loose, redundant and wrinkled skin of the distal extremities. By definition, histopathology of affected tissue reveals sparse or fragmented elastic fibers. However, this can be difficult to assess on routine staining, and sometimes requires electron microscopy. The condition has been associated with plasma cell dyscrasias or recurrent inflammatory states. We present a case of a 65-year-old man who presented with enlarged and doughy finger pads. Skin biopsy showed diffuse dermal amyloid deposition displacing dermal stroma and reduction of elastic fibers, although these changes were subtle on routine hematoxylin and eosin staining. Mass spectrometry of laser capture microdissected tissue showed AL kappa-type amyloid and further workup revealed a diagnosis of primary systemic AL-kappa amyloidosis requiring bone marrow transplantation. This case represents an unusual presentation of acquired cutis laxa and highlights the need for a high index of suspicion when reviewing histopathology of this entity. In addition, the case highlights the importance of investigation into possible systemic associations, such as plasma cell dyscrasias.     

Acquired cutis laxa associated with multiple myeloma

Cutis laxa is an uncommon condition characterized by loose and redundant skin. Biopsy results are positive for a reduction in or an absence of elastic fibers in the dermis. Cutis laxa is acquired or congenital. The acquired form is either a generalized insidious form (type I) or a form associated with prior inflammation (type II). Cardiovascular, pulmonary, gastrointestinal, and urologic complications may occur. In the past, cutis laxa was associated with plasma cell dyscrasia. We report on a characteristic cause of cutis laxa to alert clinicians to this uncommon manifestation of multiple myeloma.     

Cutis laxa associated with amyloidosis

A case of systemic amyloidosis associated with an atypical plasma cell dyscrasia is reported, in which the cutaneous amyloid deposits appeared to have caused elastolysis (cutis laxa).     

Generalized Cutis Laxa Associated with Heavy Chain Deposition Disease

BACKGROUND: Cutis laxa is a heterogeneous group of inherited and acquired disorders characterized clinically by loose skin and histologically by altered elastic tissue. Heavy chain deposition disease is a very rare monoclonal immunoglobulin disorder, distinct from multiple myeloma, in which there is production and deposition of defective immunoglobulin heavy chains without light chain deposition. OBJECTIVE: We describe a case of acquired cutis laxa associated with heavy chain deposition disease. RESULTS: A 50-year-old male presented with acute renal failure, IgG4 heavy chain deposition in the kidneys, and no evidence of multiple myeloma. Four years later, he developed generalized acquired cutis laxa, emphysema, and a peripheral polyneuropathy. On pathology, there was destruction of elastic fibers within the dermis. CONCLUSION: This case describes a previously unreported association between acquired cutis laxa and heavy chain deposition disease.     

Autosomal recessive form of congenital cutis laxa: more than the clinical appearance

Congenital cutis laxa is an uncommon disorder of generalized elastolysis. The clinical picture is characterized by inelastic, loose, hanging skin that gives the appearance of premature aging. The disease is inherited most commonly in a severe autosomal recessive form, or as a relatively benign, autosomal dominant form. There is often systemic organ involvement in patients with the autosomal recessive form. Cardiopulmonary abnormalities are common and mainly determine the prognosis and life expectancy. Pulmonary emphysema, cor pulmonale, and right-sided heart failure generally caused by pulmonary disease are often seen in infancy. Various cardiovascular abnormalities including aortic aneurysm, pulmonary artery multiple branch stenosis have been reported in patients with this form of congenital cutis laxa. We report a 10-month-old boy with the autosomal recessive form of congenital cutis laxa who had pulmonary valve stenosis. To the best of our knowledge, this is the first case of this association to be reported in the English language literature. We also emphasize the systemic complications that may be associated with congenital cutis laxa.     

Cutis laxa in a patient with 1p36 deletion syndrome

Chromosome 1p36 deletion is the most common subtelomeric deletion syndrome characterized by variable features including unique facial appearance, intellectual disability, developmental delay, cardiac defects, seizures and hypotonia. Here, we report a patient with developmental delay, dilated cardiomyopathy, seizures, hirsutism and cutis laxa who was diagnosed with 1p36 deletion syndrome by chromosome microarray analysis. This patient is the first reported case of 1p36 deletion syndrome associated with cutis laxa and our results suggest that the 1p36 region contains one or more genes relevant to cutis laxa. This case also indicates the importance of considering chromosome abnormalities (microdeletion/microduplication syndromes) in patients presenting skin disorders combined with unexplained developmental delay, intellectual disability or multiple congenital abnormalities.     

Acquired cutis laxa and multiple myeloma

We report a patient with acquired cutis laxa and multiple myeloma, and the possible association between the two conditions is discussed.     

Cutis laxa in seven members of a north-Indian family

Congenital cutis laxa, characterized by cutaneous laxity and loose skin, may be autosomal dominant or autosomal recessive. The autosomal dominant variety is usually not associated with any systemic defects and has a good prognosis. We report an unusual family in which seven members were affected by the autosomal dominant variant of this disorder. We suggest that close monitoring of the cardiorespiratory systems may be worthwhile to detect any systemic complications, although these complications are rare in the autosomal dominant variant of cutis laxa.     

Unusual clinical presentation of amyloidosis: bilateral stenosis of the external auditory canal, hoarseness and a rapid course of cutaneous lesions

We report a patient with multiple myeloma associated with primary systemic amyloidosis who had a rapid evolution and a very unusual form of presentation. The association of amyloidosis in patients with multiple myeloma is 15%, and clinically evident mucocutaneous involvement occurs in up to 40% of patients.     

Bilateral Congenital Entropion with Cutis Laxa

Cutis laxa is a rare connective tissue disorder characterized by redundant and pendulous skin due to a defect in the elastic fiber network. Two cases of entropion associated with cutis laxa have been reported, although entropion was due to elongation of the anterior lamella or horizontal lid laxity. Thorough systemic and ophthalmic evaluations were performed, as well as chart review for the perinatal period. Surgical correction of entropion through posterior tarsotomy was done. An infant boy with dysmorphic features and furrowing of the skin of the entire body without hyperelasticity, which is typical for cutis laxa, presented with bilateral congenital entropion. We report here for the first time a different etiology of congenital entropion with cutis laxa: the eyelashes were abnormally directed due to the unusual location of their roots, which were embedded within the tarsus. Moreover, this is the only case of cutis laxa with congenital entropion involving both upper and lower eyelids. Congenital entropion can be associated with cutis laxa. Although elongation of the anterior lamella and horizontal lid laxity predispose to such an entropion, abnormal location of the roots of the eyelashes might be encountered and marginal eyelid rotation surgery is indicated.     

Penicillamine-induced Elastosis Perforans Serpiginosa and Cutis Laxa in a Patient with Wilson's Disease

Elastosis perforans serpiginosa (EPS) is a rare reactive perforating dermatosis that is characterized by the transepidermal elimination of abnormal elastic fibers. Penicillamine, which is one of the clear triggers for EPS, is a heavy metal chelator that is primarily used for disorders such as cystinuria and Wilson''s disease. It may cause alterations in the dermal elastic tissue such as pseudo-pseudoxanthoma elasticum, acquired cutis laxa, EPS and anetoderma. Herein we present a case of cutis laxa and EPS in a 34-year-old man who was previously on a long-term, high-dose of penicillamine for Wilson''s disease. The combination of EPS and cutis laxa induced by penicillamine has rarely been reported and we report the first such case in Korea.     

Cutis laxa in hereditary gelsolin amyloidosis

BACKGROUND: Hereditary gelsolin amyloidosis (AGel amyloidosis) is an age-associated systemic disease with global distribution, caused by a G654A or G654T gelsolin gene mutation. Cutis laxa is a principal clinical manifestation of this disease. However, only few data on the dermatological involvement are available, and the pathogenesis of this amyloidosis-associated form of cutis laxa has remained unknown. OBJECTIVES: To elucidate the pathomechanism of this less well-known genodermatosis. METHODS: We performed systematic clinical, histological, immunohistochemical and ultrastructural skin biopsy studies in 12 patients with a G654A gelsolin gene mutation. For comparison, skin specimens from 10 control subjects were analysed. RESULTS: All patients had clinically characteristic cutis laxa, and frequently other signs of symptomatic skin disease such as increased fragility and risk for intracutaneous bleeding. All patients showed cutaneous deposition of gelsolin amyloid (AGel), mainly attached to basement membranes or basal laminae of various cutaneous structures, dermal nerves and blood vessel walls, and elastic fibres, particularly in the lower reticular dermis. AGel often encircled the elastic fibres, and colocalized with amyloid P component (AP), an elastic fibre microfibrillar sheath-associated protein. Fragmentation and loss of elastic fibres, epidermal atrophy, and reduction of dermal appendages were also common. Antibodies to wild-type gelsolin bound to S-100-positive epidermal dendritic cells, a previously unrecognized immunoreaction. Patients had fewer gelsolin-positive dendritic cells than controls. CONCLUSIONS: Widespread skin involvement with AGel deposition and elastic fibre involvement are essential pathological features in AGel amyloidosis, and contribute to the characteristic cutis laxa, dramatic in old age. Codistribution of AGel and AP, with demonstrated specific binding affinity for amyloid fibrils, suggests that elastic fibre-associated AP acts as a matrix for cutaneous amyloid deposition in AGel amyloidosis.     

Acral localized acquired cutis laxa

We report the first case of acral localized acquired cutis laxa. The skin laxity was preceded by swelling of the fingers and toes and by the appearance of papular urticaria. Dapsone therapy was effective in controlling the swelling. Examination of skin biopsy specimens showed fragmentation and almost total loss of elastic fibers in the areas of cutis laxa. Electron microscopy showed no abnormalities in elastic structure and function in unaffected skin. In addition, electron microscopic examination of an urticarial lesion showed a neutrophilic dermatosis with polymorphonuclear leukocytes attached to the surface of either normal elastic fibers or fibers showing early degenerative changes. These findings suggest that there is no primary defect in the elastic fibers and that the polymorphonuclear leukocytes play a significant role in the destruction of the elastic fibers and the subsequent development of cutis laxa in this case.     

Localized axillary milia en plaque: a rare cutaneous case presentation of systemic amyloidosis

Systemic AL amyloidosis is known to be associated with plasma cell dyscrasias, including multiple myeloma. The cutaneous manifestations of systemic AL amyloidosis are varied, but typically include waxy plaques or subcutaneous nodules. We report a woman who presented with bilateral eruptions of hyperpigmented plaques in her axillae, which were diagnosed as milia en plaque. She had a history of multiple myeloma, for which she was under the care of a haematologist. This is the first documented case, to our knowledge, of an eruption in the axillae being milia en plaque.     

Congenital generalized cutis laxa: 5 cases]

BACKGROUND: Congenital cutis laxa is an exceptional condition. No large scale series has been reported in the French literature. We report 5 cases observed between 1993 and 1997. PATIENTS AND METHODS: Five children with a morphotype compatible with congenital generalized cutis laxa were examined. A family study, complete visceral workup and skin biopsy with standard histology, orceine coloration and histomorphometric analysis of the collagen and elastic fibers of the dermis were performed. Karyotype and copper metabolism (cupremia and ceruloplasminemia) were available in 3 children. RESULTS: The diagnosis was clinical and proven histologically by orceine coloration of skin biopsies in all cases. There were discrete ultrastructure anomalies in the pure cutaneous form expressed in case n(o) 1 with possible autosomal dominant inheritance. Cupremia and ceruloplasminemia were normal in the 3 children explored; this corresponds to absence of the Elhers-Danlos type IX phenotype. The karyotype was normal in 3/3 children, in agreement with the absence in these three children of marfanoid cutis laxa phenotype. Patients n(o) 2, 3, 4 and 5 had common features: probable autosomal recessive inheritance and severe prognosis. Patient n(o) 2 died at the age of 3 weeks and had severe pulmonary emphysema. This child's sister also had cutis laxa but with no visceral component (autosomal recessive inheritance with variable expression). Patients n(o) 3, 4 and 5 had a severe multiple malformative syndrome with facial dysmorphism, growth retardation, unexplained digestive disorders and psychomotor retardation. DISCUSSION: Our series of 5 patients and data in the literature confirm that primary cutis laxa is a heterogeneous group of conditions both clinically and genetically. The anomalies associated in patients n(o) 3, 4 and 5 were not directly related to anomalous elastic tissue as was also the case for the craniostenosis in patient n(o) 3 reported in other cases in the literature.     

Acquired localized cutis laxa confined to the face: case report and review of the literature

BACKGROUND: Cutis laxa is an uncommon entity characterized by laxity of the skin, which hangs in loose folds, producing the appearance of premature aging. It can be subdivided into congenital and acquired. This latter variant is rare and the skin involvement varies from generalized to localized. We report a case of a localized acquired cutis laxa confined to the face, without preceding inflammatory lesions or systemic compromise. Four similar cases have been reported to date. The etiology remains unknown and there is no definitive treatment. METHODS: A 27-year-old White woman came to our hospital with a wrinkled face, pendulous earlobes and drop eyelids. Changes began 5 years prior, and she appeared much older than her age. RESULTS: Histological analysis and ultrastructural examination of skin biopsy revealed reduction and fragmentation of elastic fibers, confirming the diagnosis of cutis laxa. No systemic involvement was diagnosed. The patient was submitted to plastic surgery for repair, with satisfactory results to date. CONCLUSIONS: Acquired localized cutis laxa confined to the face without preceding inflammatory lesions is extremely rare. The etiology remains unknown. Clinical features and histopathologic findings confirm the diagnosis. Surgical repair seems to be the only therapeutic choice, but the results are variable and temporary.     

Nail dystrophy and blisters as sole manifestations in myeloma-associated amyloidosis

We report the case of a 61-year-old Japanese man with IgG lambda-type multiple myeloma, who presented with nail dystrophy as the initial manifestation of systemic amyloidosis. Subsequently he developed bullous amyloidosis. This report documents these two rare signs of systemic amyloidosis and demonstrates the precise location of cutaneous blister formation and amyloid deposition by fluorescence antigen mapping and electron microscopy.     

Cutis laxa of the autosomal recessive type in a consanguineous family

Cutis laxa comprises a group of uncommon disorders of elastin fibers first described by Graf in the early 19th century. The main characteristic is a redundant, loose skin with deep wrinkling or sagging combined with a variable systemic involvement. Histopathologic examination presents various abnormalities of the elastin fibers. We distinguish congenital as well as acquired forms of generalized or localized cutis laxa. The mode of inheritance shows great heterogeneity: autosomal dominant, autosomal recessive and X-linked recessive inheritance have all been described. We present a severe case of autosomal recessive type 1 cutis laxa in a female patient, born in a large, consanguineous Turkish family, where three other family members had already died of the disease. A missense mutation of fibulin-5 was identified in this patient.