Myeloma-associated systemic amyloidosis presenting with acquired digital cutis laxa-like changes

A 59-year-old woman presented with a 6-year history of lax skin on the distal fingers of both hands, as well as a recent increase in the size of her tongue. Histopathology of skin from her distal finger showed amyloid deposition and bone marrow biopsy revealed an underlying plasma cell dyscrasia. Initial treatment with cyclophosphamide, vincristine, adriamycin and methylprednisolone has produced a significant reduction in the swelling of both her hands and tongue. Acquired digital cutis laxa-like changes are a rare cutaneous manifestation of systemic amyloidosis.     

获得性局限性皮肤松弛症

报告1例获得性局限性皮肤松他症。患者男,31岁。有臀部局部皮肤明显松弛、肤色加深2年,无任何自觉症状。皮损组织病理检查示弹性纤维明显减少,形态异常,有断裂。给予整形手术治疗。     

获得性皮肤松弛症

报告1例获得性皮肤松弛症。患者女,17岁。面颈、双腋窝及股部皮肤松弛2年。皮肤科检查:面颈、双腋窝及股部皮肤明显松弛,皱纹密集,皮沟加深,无弹性。左颈部皮损组织病理示:表皮厚度大致正常,网篮状角化,真皮浅层血管周围少量淋巴细胞浸润。弹性纤维染色示:真皮浅层弹性纤维数量明显减少、形态异常。诊断:获得性皮肤松弛症。     

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.     

Protein AL origin in amyloidosis cutis nodularis atrophicans

A case of amyloidosis cutis nodularis atrophicans (ACNA) was reported. The characteristics of the amyloid deposit were examined using the unlabeled immunoperxoidase method (peroxidase-antiperoxidase method, so called PAP). The study revealed that the amyloid deposit contained A type protein AL, and the surrounding plasma cells contained λ and κ types of both immunoglobulin light chains and Bence Jones protein, with strong preference toward the λ type of each protein. These results suggest that, in ACNA, the plasma cells produce and secrete immunoglobulin light chains and/or Bence Jones protein, and that the protein degenerates into protein AL and then accumulates in the tissue to form nodules. ACNA seems to be a localized form of AL type amyloidosis, since patients with ACNA have no signs of systemic involvement.     

Fractional photothermolysis treatment of digital cutis laxa reverses hand disability

In this case study, we present a safe and novel treatment for a patient with soft tissue hand disability caused by severe and chronic lupus and cutis laxa (CL). This patient was a woman in her 50s with a 20‐year history of systemic lupus erythematous (SLE) and multiple sclerosis who developed hand disability because of the drastic loss of firmness in her soft tissue, extending from the dermis down to the ligaments. The likely cause was CL with SLE synovitis, exacerbated by corticosteroid tapering. Fractional photothermolysis (FP) LASER (Fraxel DUAL 1550/1927; Solta Medical) therapy profoundly alleviated her joint locking in addition to improving the firmness of the overlying skin to reverse her hand disability. This case illustrates a novel approach to CL hand treatment and the profound impact the treatment had on the patient's disabled hand. FP therapy is quick and safe, and its medical application to skin and joints should be further explored.     

9例色素异常性皮肤淀粉样变患者GPNMB基因序列分析

目的:研究色素异常性皮肤淀粉样变(ACD)患者的临床特征及GPNMB基因突变情况.方法:回顾性分析9例ACD患者的临床资料,对患者及部分患者父母进行GPNMB基因检测和序列分析,采用Mutation-Taster预测突变位点的致病性.结果:9例患者中:c.565C>T纯合突变6例,其中4例经家系验证符合常染色体隐性遗传...     

青春期后发病的色素异常性皮肤淀粉样变家系相关基因突变研究

目的:青春期后发病的色素异常性皮肤淀粉样变少见,本文报道一家系,并检测该家系中OSMR及IL31RA基因的突变情况。方法:经知情同意后采集该先证者及家系4例患者外周血后用PCR扩增OSMR基因第12～15号外显子和IL31RA基因12号外显子并进行测序。结果:该家系所有成员OSMR基因第12～15号外显子和IL31RA基因第12号外显子均未发现明显突变。结论:该家系未在OSMR基因第12～15号外显子和IL31RA基因第12号外显子发现突变,可能存在其他基因突变位点有关,需要进一步验证。     

Purpuric halo around hemangioma as a clue for primary systemic amyloidosis: Case report and review of literature

Mucocutaneous lesion appears in up to 40% of patients with primary systemic amyloidosis (AL amyloidosis). The cutaneous signs may be co-expressed with other organ involvement or even solely presented as the first clue. We reported a case of systemic AL amyloidosis who was initially presented as a solitary hemangioma with a purpuric halo. Excisional biopsy revealed a hemangioma with amyloid deposited in thickened vascular walls. Systemic AL amyloidosis was diagnosed after thorough survey. The stage of disease at the time of initial treatment is the greatest prognostic factor. To our knowledge, this is the first case of systemic AL amyloidosis initially presented as a purpuric halo around hemangioma in Taiwan. This target-like lesion should be linked to systemic AL amyloidosis and early diagnosis is extraordinary important.     

Case of primary localized cutaneous amyloidosis with protean clinical manifestations: lichen, poikiloderma-like, dyschromic and bullous variants

Primary localized cutaneous amyloidosis (PLCA) commonly presents as macular and lichen variants. We present a case of a 27-year-old Chinese woman with cutaneous features of the rarely reported poikiloderma-like, dyschromic and bullous forms of PLCA, and the commoner lichen variant. There were no syndromic associations or systemic involvement, and the various morphological subtypes occurred in isolation from one another. We review the clinical spectrum of PLCA, highlight its protean clinical manifestations in this patient, and discuss its postulated pathogenesis in relation to its histopathological features.     

The complexity of elastic fibre biogenesis in the skin – a perspective to the clinical heterogeneity of cutis laxa

Elastic fibres are critical connective tissue components providing elasticity and resilience to skin and other tissues. These fibres are composed of elastin and a number of elastin‐associated microfibrillar proteins that assemble in a complex fibre network in a multi‐step process. Multiple cellular processes, including mitochondrial function, specific molecules in the secretory pathways and temporally and spatially ordered production of elastic fibre components, are required for the biogenesis of functional elastic fibres. Abnormalities in these processes can lead to loss of functional elastic fibres manifesting phenotypically as a skin disease. The paradigm of elastic fibre diseases affecting the skin is cutis laxa, a clinically and genetically heterogeneous group of disorders characterized by loose and sagging skin, frequently associated with extracutaneous manifestations in the lungs and the arterial blood vessels. The complexity of cutis laxa is emphasized by the fact that as many as 10 distinct genes can harbour mutations in this and related disorders. Understanding of the pathomechanistic pathways involved in perturbed elastic fibre assembly in cutis laxa provides information potentially helpful for the development of molecular strategies towards treatment of these, currently intractable, diseases.     

ATP6V0A2‐related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype

In ATP6V0A2‐related cutis laxa, the skin phenotype varies from a wrinkly skin to prominent cutis laxa and typically associates with skeletal and neurological manifestations. The phenotype remains incompletely characterized, especially in adult patients. Glycosylation defects and reduced acidification of secretory vesicles contribute to the pathogenesis, but the consequences at the clinical level remain to be determined. Moreover, the morphology of the elastic fibres has not been studied in ATP6V0A2‐related cutis laxa, nor its relation with potential clinical risks. We report on the extreme variability in ATP6V0A2‐related cutis laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand disease and hypothesize on the pathogenesis that might link both with deficiency of glycosylation and with elastic fibre anomalies. Our data will affect clinical management of patients with ATP6V0A2‐related cutis laxa.     

Pernio as the presenting sign of blast crisis in acute lymphoblastic leukemia

A previously healthy 5‐year‐old girl presented with acute onset of blue toes and red spots on the nose and fingers. The striking nature of these lesions, along with the finding of submandibular lymphadenopathy, prompted further evaluation. Laboratory findings were remarkable for anemia, high transaminase levels, and high blast count. Histopathologic findings were consistent with early pernio. Further examination revealed acute B‐cell lymphoblastic leukemia. Treatment of the leukemia led to resolution of the pernio.     

An unusual form of primary systemic amyloidosis: amyloid elastosis: report of a case treated by haematopoietic cell transplantation

Amyloid elastosis is a rare variant of primary systemic amyloidosis characterized by amyloid deposited around elastic fibres. Only two cases, with pseudoxanthoma elasticum-like features and fatal outcome, have been reported. A 56-year-old woman presented with polyneuropathy and a diffuse plane xanthoma-like eruption. Light and electron microscopy studies revealed deposits of amyloid L encasing either normal-looking or short, fragmented elastic fibres in the dermis in a pattern characteristic of amyloid elastosis. The patient had medullary plasmocytosis with lambda light chain restricted expression and underwent autologous stem cell transplantation, which resulted in progressive regression of mucocutaneous signs and stabilization of the polyneuropathy. Our case extends the spectrum of clinical and histopathological presentations of amyloid elastosis. Haematopoietic cell transplantation might improve outcome in patients with multisystem disease.     

Extravascular necrotizing palisaded granulomas as the presenting skin sign of systemic lupus erythematosus

We recently examined a patient who presented clinically with tender, erythematous papules associated with a febrile illness and polyarthralgias. Histopathological examination revealed extravascular palisaded neutrophilic granulomas, a skin reaction pattern originally described in Churg-Strauss disease but subsequently observed in a variety of other systemic disorders characterized by immune complex generation. A diagnosis of systemic lupus erythematosus (SLE) was established. To our knowledge, this is the first report of extravascular necrotizing palisaded granulomas as the presenting skin sign of SLE.     

Aleukaemic leukaemia cutis as an initial manifestation of myeloid/NK cell precursor acute leukaemia

Aleukaemic leukaemia cutis is a rare condition characterized by infiltration of leukaemic cells into the skin before they appear in the peripheral blood. We report a case of an aleukaemic leukaemia cutis, which had a history of exposure to atomic bomb radiation. A 57-year-old Japanese woman initially presented with a 20-week history of multiple red papules and plaques mainly over the trunk. Histological examination revealed the infiltration of atypical monocytic cells in the dermis, but no leukaemic cells were detected in the peripheral blood. Twenty-three weeks after the appearance of the eruption, leukaemic cells were detected in the peripheral blood for the first time. The results of immunohistochemistry of the skin biopsy specimen and flow cytometry of the peripheral blood indicated the rare phenotype of myeloid/NK cell precursor acute leukaemia. This is the first case report of myeloid/NK cell precursor acute leukaemia presenting as aleukaemic leukaemia cutis in the English literature, and awareness of this clinical presentation may be important to reach the correct diagnosis.