[Multifocal chalazodermic amyloidosis: The concept of immunoglobulinemic elastopathy]. / Chalazodermie amyloïde multifocale. Le concept d'élastopathie immunoglobulinémique.

INTRODUCTION: Impairment of dermal elastic tissue occurs in different entities associated with immunoglobulins or immunoglobulin-derived protein-secreting clonal plasma cell proliferations, such as amyloid elastosis, anetodermic nodular amyloidosis or monoclonal gammopathy-associated cutis laxa. We report a case of cutaneous immunoglobulinemic amyloidosis revealed by a unique chalazodermic presentation and we review elastic tissue impairment in patients with monoclonal gammopathies. OBSERVATION: A 67-year-old woman consulted for non-infiltrated anetodermic lesions on the upper left quadrant of her abdomen present for ten years. She also had a chalazodermic plaque with abnormal skin wrinkling and laxity in her right axilla. Biopsies revealed deep dermal and subcutaneous amyloid deposits. Immunohistochemistry with lambda light chain was positive. Orcein staining and electron microscopy showed extensive elastolysis. The patient presented no signs of systemic involvement, but a very small amount of monoclonal IgGλ gammopathy was detected during follow-up. DISCUSSION: This is a unique chalazodermic presentation of immunoglobulinemic amyloidosis that does not fit into a clearly-defined nosological setting. It highlights the complex interactions between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to different types of impairment of the latter. We therefore suggest the unifying concept of immunoglobulinemic elastopathy, underscoring the need to screen for monoclonal gammopathy in patients presenting elastic tissue impairments.

[Skin manifestations of monoclonal gammopathies]. / Manifestations cutanées associées aux gammapathies monoclonales.

Whatever their aetiology, monoclonal gammopathies can be associated to several clinical features. Mechanisms are various and sometimes unknown. Skin is frequently involved and may represent a challenging diagnosis. Indeed, skin manifestations are either the presenting features and isolated, or at the background of a systemic syndrome. Our objective was to review the various skin manifestations that have been associated with monoclonal gammopathies.

Acquired cutis laxa with an interstitial granulomatous reaction associated with IgG lambda monoclonal gammopathy.

Acquired cutis laxa (ACL) is a rare connective tissue disorder that affects the skin elastic fibers, resulting in the loss of elasticity. In 50% of cases, this condition is associated with other diseases, particularly plasma-cell dyscrasias. This report describes a case of ACL with unusual clinical and histopathological characteristics. A 29-year-old man presented with diffuse erythematous plaques that had first appeared 5 months previously. Examination revealed multiple flaccid erythematous plaques on his trunk, neck, and skinfolds. Immunophenotyping of bone marrow aspirate revealed 7% of monoclonal plasma cells with lambda light chain expression. Skin biopsy histology revealed foci of interstitial granulomatous reaction. Weigert stain showed a loss of elastic fibers in the dermis, areas with thickened fibers and elastophagocytosis. Immunohistochemistry was positive for CD68. The cutaneous findings enabled an early diagnosis of IgG lambda monoclonal gammopathy to be made. Microscopic examination revealed an interstitial granulomatous reaction and severe alterations in the elastic fibers that varied in intensity in the different biopsies. Curiously, little has been mentioned in the literature regarding the presence of an interstitial granulomatous reaction in ACL. It is our belief that this reaction is secondary to the degenerative process of the elastic fibers.

Ultrastructural demonstration of a relationship between acquired cutis laxa and monoclonal gammopathy.

Acquired cutis laxa is an uncommon disorder sometimes associated with monoclonal gammopathy and multiple myeloma, although the mechanism of this link is unclear. We report here a case of a 34-year-old man with generalized acquired cutis laxa and monoclonal light chain disease with renal and neurological involvement. Electron microscopy examination of a skin sample revealed shortened and fragmented elastic fibres in the reticular dermis and normal collagen bundles. Immunogold labelling revealed anti-lambda antibodies closely bound to the microfibrillar component of elastic fibres, thus supporting a causal relationship between monoclonal gammopathy and the changes in skin elasticity.

Acquired cutis laxa associated with heavy chain deposition disease.

Acquired cutis laxa (generalized acquired elastolysis) is a condition of unknown etiology characterized by a degeneration of elastic fibers in the skin, resulting in laxity with reduced elastic recoil. We describe a patient with acquired cutis laxa associated with an underlying heavy chain deposition disease. Direct immunofluorescence testing of lesional skin demonstrated immunoglobulin G deposition on elastic fibers, suggesting that in some cases, cutis laxa may have an immune-mediated etiopathogenesis.

Bilateral blepharochalasis.

Blepharochalasis is a rare disorder characterized by recurrent painless periorbital oedema, which leads to atrophy of the periorbital skin. Pathomechanism of the disease is probably immunological with a nearly complete loss of elastic fibres. The authors describe a 17-year-old woman, who was followed for 7 years. IgA deposits were found in the periorbital tissues, which confirm the immunological background of the condition. Electron microscopy results show that not only elastic but also collagen fibres were affected.

[Unilateral blepharochalasis with IgA-deposits]. / Unilaterale Blepharochalasis mit läsionalen IgA-Ablagerungen.

A 36-year-old male patient presented with unilateral periocular skin atrophy. The blepharochalasis developed without any obvious inflammation of the eyelids over the past 10 years. Interestingly, elongated blood vessels and microaneurysmatic vessel changes were found in the tarsal conjunctiva. A punch biopsy revealed a nearly complete loss of elastic fibres in the papillary and superficial reticular dermis. The contralateral side was histopathologically normal. On immunohistology IgA-deposits could be observed especially on perifollicular elastic fibres. Immunoelectronmicroscopy confirmed the diagnosis and suggested fibulin and fibronectin as potential binding sites for the autoantibodies. This further report of elastolysis in association with IgA-autoantibodies defines the autoantibody binding site in more detail and suggests that the immune mechanisms may also play a role in vessel changes of the conjunctiva.

Middermal elastolysis in two patients with lupus erythematosus.

Despite lupus erythematosus (LE) being considered a "connective tissue disease," little has been written about the elastic fiber changes in the skin of affected patients. We report our histologic findings in two patients with unusual cutaneous lesions. Elastic fiber loss was noted, and scattered giant cells with elastic fiber phagocytosis were prominent in one patient. The findings are similar to those described for middermal elastolysis. Other authors have reported patients with LE and elastic fiber loss resembling anetoderma. We believe that a spectrum of elastic fiber changes can occur in patients with LE and may be induced by infiltrating lymphocytes and/or circulating antibodies.

Cutis laxa acquisita: is there any association with Borrelia burgdorferi?

We report the first case of an acquired form of generalized cutis laxa which has positive serology and a positive polymerase chain reaction (PCR) result for lyme borreliosis. A 44-year-old man complained of excessively loose skin for four years and had no family history of any skin disease. Dermatological examination showed lax and wrinkled skin all over the body (especially on the cheeks and the intertriginous areas). Positive serology for lyme borreliosis and the presence of Borrelia burgdorferi DNA which was demonstrated by nested PCR in this acquired form of cutis laxa is interesting since it has not been reported in literature previously.

Immunoglobulin A (IgA) deposits in lesional skin of a patient with blepharochalasis.

We describe a 21-year-old male patient with blepharochalasis, a form of localized acquired cutis laxa. He had a 13-year history of recurrent swelling attacks of the eyelids of unknown origin leading to periocular localized cutis laxa. Histology of lesional skin confirmed almost complete loss of elastic fibres in the reticular and papillary dermis. Immunofluorescence and immunoelectron microscopy studies showed abundant immunoglobulin A (IgA) deposits around the remaining elastic fibres. Control skin of the forearm was negative. These findings support the hypothesis that immunopathogenetic mechanisms may contribute to the elastolytic process of blepharochalasis.

Acquired cutis laxa associated with a plasma cell dyscrasia.

Acquired cutis laxa (generalized acquired elastolysis) is characterized by skin laxity often with systemic involvement of the lungs, aorta, gastrointestinal tract, and pelvic organs. Although there have been many speculations regarding its pathogenesis, the etiology of this condition is still unclear. We describe a patient with generalized acquired cutis laxa associated with a plasma cell dyscrasia. Immunofluorescence studies were used to evaluate the pathogenesis of the elastolysis. Lesional skin was examined by direct and indirect immunofluorescence techniques for evidence of deposition of immunoglobulins on elastic fibers in the dermis. Direct immunofluorescence revealed deposition of IgG on elastic fibers in the dermis. Some patients with acquired cutis laxa have underlying lymphoreticular disorders such as plasma cell dyscrasia and may have immunoglobulins deposited on dermal elastic fibers. Immune-mediated mechanisms may play a major role in the pathogenesis of acquired cutis laxa in at least some cases.

[Acquired generalized cutis laxa with paraproteinemia (IgG lambda). Immunofluorescence study, clinical and histologic findings with review of the literature]. / Erworbene generalisierte Cutis laxa mit Paraproteinämie (IgG-lambda). Immunfluoreszenzstudie, Klinischer und histologischer Befund mit Literaturübersicht.

A 49-year-old patient developed acquired generalized cutis laxa, manifest as involvement of the elastic fibres of the dermis and the internal organs, leading to pulmonary emphysema, bilateral inguinal hernia and two oesophageal diverticula. The patient's serum levels of IgG lambda paraprotein were elevated. Direct immunofluorescence examination revealed intensive linear deposits of IgG lambda light chains, an early component of complement C1q and discrete C3 deposits. The deposits were found along the preserved elastic fibres in the dermis, especially in the papillary dermis, at the dermoepidermal junction around the sweat and sebaceous glands and in the walls of small vessels. Dermal alterations of this kind have not been described previously.

Anetoderma of Jadassohn-Pellizzari.

Anetoderma (derived from the Greek anetos, meaning slack) is a term used to describe localized increased laxity of the skin with herniation or outpouching, resulting from abnormal dermal elastic tissue. Primary anetoderma is distinctly rare. We describe a case where we suspect an auto-immune aetiology.

Features of an autoimmune process in mid-dermal elastolysis.

Mid-dermal elastolysis is a rare disorder that is manifested clinically by wrinkling and histologically by the selective absence of elastic fibers in the mid dermis. We describe a young woman who developed abnormal wrinkling after augmentation mammoplasty with silicone implants. Histologic examination confirmed the diagnosis of mid-dermal elastolysis. In addition, a positive antinuclear antibody titer and a false-positive Lyme titer were subsequently detected. In a previously reported case a patient who had mid-dermal elastolysis also had an unusual false-positive pattern for Lyme disease. Silicone mammoplasty has been associated with connective tissue diseases. This report adds mid-dermal elastolysis to the list of diseases associated with augmentation mammoplasty and, along with the presence of autoantibodies, supports autoimmune involvement in mid-dermal elastolysis.

Acquired cutis laxa concomitant with nephrotic syndrome.

A 41-year-old woman developed laxity and wrinkling of the skin. This process spread slowly to involve the skin of almost the entire body, without any previous inflammatory skin disorder. The skin of her face, neck, and trunk hung in loose folds, leading to a prematurely aged appearance. One year later she noticed edema on her face and legs. Laboratory studies disclosed low C3 and CH50 serum levels and proteinuria. Skin biopsy specimens revealed extensive loss and fragmentation of dermal elastic fibers. A renal biopsy specimen showed membranoproliferative glomerulonephritis (type 2), and an immunofluorescent study disclosed C3 and IgG deposition in the mesangial matrix and along the glomerular basement membrane. We propose that, in this case, cutis laxa may be related to an abnormal immune response.

Biochemical, morphological and immunological findings in a patient with a cutis laxa-associated inborn disorder (De Barsy syndrome).

Clinical symptoms of a male infant are described and compared with cases now classified as the De Barsy syndrome, a distinct disorder related to cutis laxa. Morphologically, elastic fibres in skin were frayed and reduced in number and density. The collagen fibril network was normal. Biochemical studies on collagen metabolism in a skin specimen and in cultured skin fibroblasts showed a normal amino acid content and a normal electrophoretic pattern of collagen constituents. The chemotactic migration of cultured fibroblasts was diminished when compared with fibroblasts from donors of different age groups. Immunological investigations revealed an imparied granulocyte function.