Systemic amyloidosis presenting with glans penis involvement

Penile amyloidosis has been reported on many occasions in the literature, but all of these have been forms of primary cutaneous amyloidosis. Systemic amyloidosis presenting with a penile ulcer as the first manifestation has not previously been reported. We present two patients in whom an ulcer of the glans penis was the first complaint that led to a diagnosis of systemic amyloidosis. In both patients, lambda light chain type amyloid was showed immunohistochemically. Both patients presented with other manifestations of systemic amyloidosis, including nail dystrophy characterized by onycholisis, trachyonychia and onychoschizia.     

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.     

Systemic amyloidosis with an underlying lymphoproliferative disorder

A case of systemic amyloidosis with an underlying lymphoproliferative disorder is described. Nail changes, which included longitudinal striation, crumbling and brittleness were striking and preceded the appearance of other cutaneous lesions by a period of 5 months. A nail biopsy confirmed the presence of amyloid deposits in the nail fold and distal part of the nail bed.     

Nodular amyloidosis: review and long-term follow-up of 16 cases

OBJECTIVES: To review the clinical presentations of nodular amyloidosis, examine these cases for evidence of plasma cell monoclonality, and obtain long-term follow-up data on progression to systemic amyloidosis. DESIGN: Retrospective case series with long-term follow-up data obtained by phone survey. SETTING: Mayo Clinic, Rochester, Minn, and Mayo Clinic, Jacksonville, Fla. PATIENTS: All patients diagnosed with nodular amyloidosis between 1971 and 2001. MAIN OUTCOME MEASURES: Clinical records and histopathologic characteristics were reviewed. Polymerase chain reaction to assess immunoglobulin gene rearrangement and immunohistochemical analysis to detect kappa and lambda light chain restriction were performed on paraffin-embedded specimens. Patients were contacted by phone to determine if progression to systemic disease had occurred. RESULTS: We identified 16 patients with nodular amyloidosis. Mean age at diagnosis was 60.8 years (range, 41-87 years). Eight (50%) of 16 patients had acral involvement. Immunohistochemical analysis demonstrated light chain restriction in 6 of 10 patients. At the time of diagnosis, no patient was known to have systemic amyloidosis. One patient, however, had a serum monoclonal lambda protein and died 4 years later secondary to systemic amyloidosis. Follow-up data were obtained in 14 of the remaining 15 patients, with a mean follow-up time of 10 years (range, 8 months to 24 years). None of the 14 patients had signs or symptoms suggesting progression to systemic amyloidosis. CONCLUSIONS: Nodular amyloidosis affects both sexes during middle age, with a tendency to affect acral sites. The relatively high rate of light chain restriction in our series provides further evidence for the presence of a local plasma cell clone. Progression to systemic amyloidosis is uncommon.     

以肌病为首发表现的系统性淀粉样变性一例

目的 探讨系统性淀粉样变性的临床病理特点,鉴别诊断,治疗与预后.方法 分析我科收治的1例以肌肉表现为首发症状的系统性淀粉样变性的临床、病理、实验室检查特点,并对文献进行复习.结果 该患者以全身肌肉变硬、巨舌为首发症状,检查进一步发现心血管系统、呼吸系统、消化系统、肾脏受累.经皮肤、肌肉、胃肠黏膜组织病理H-E染色、刚果红染色、偏振光显微镜检查证实为系统性淀粉样变性.结论 系统性淀粉样变性可以肌肉病变为首发表现.     

Nail abnormalities and scleroderma-like lesions on the face associated with systemic amyloidosis

INTRODUCTION: Mucocutaneous involvement in systemic amyloidosis occurs in 29 to 40 p. 100 of cases. Nail abnormalities are infrequent in AL amyloidosis. We report an original case of AL amyloidosis associated with cutaneous and integument alterations and scleroderma-like infiltration of the face. CASE REPORT: A 73 year-old woman was hospitalized because of weight loss and asthenia. She had been treated 4 years earlier with chemotherapy for a IgG-type multiple myeloma with complete resolution of the underlying monoclonal gammapathy. Cutaneous examination showed nail dystrophy of all fingernails associated with scleroderma-like skin changes on the chin and lips. Histopathologic study of a chin biopsy confirmed the presence of amyloid deposits in the dermis. Laboratory data were normal, without signs of recurrence of multiple myeloma. DISCUSSION: We report an original case of a patient who developed two unusual cutaneous manifestations associated with AL amyloidosis. Moreover, there was no correlation between the severity of the cutaneous lesions and the extent of the underlying hematological disease.     

Longitudinal Erythronychia

Longitudinal erythronychia is a linear red band on the nail plate that originates at the proximal nail fold, traverses the lunula, and extends to the free edge of the nail plate. Longitudinal erythronychia is classified based upon the number of nails affected and the number of red streaks present on each nail as follows: type Ia (monodactylous - single band), type Ib (monodactylous - bifid bands), type IIa (polydactylous - single band), and type IIb (polydactylous - multiple bands). Associated morphologic findings that can be present at the distal tip of the nail with longitudinal erythronychia include fragility, onycholysis, splinter hemorrhage, splitting, subungual keratosis, thinning, and V-shaped nick. Some patients with longitudinal erythronychia seek medical evaluation because of pain in the associated distal digit; however, the linear red nail plate dyschromia is often asymptomatic and the individual is concerned about the cosmetic appearance or distal nail fragility. Longitudinal erythronychia can be a clinical manifestation of an underlying local or systemic condition. Benign tumors (glomus tumor, onychopapilloma, and warty dyskeratoma), malignant neoplasms (malignant melanoma and squamous cell carcinoma), and other conditions (hemiplegia and postsurgical scar) can be associated with monodactylous longitudinal erythronychia or it may be idiopathic or the initial stage of polydactylous longitudinal erythronychia-associated systemic conditions. Polydactylous longitudinal erythronychia is most commonly reported in patients with Darier disease (keratosis follicularis); other associated conditions include acantholytic dyskeratotic epidermal nevus, acantholytic epidermolysis bullosa, acrokeratosis verruciformis of Hopf, amyloidosis, graft-versus-host disease, lichen planus, and pseudobulbar syndrome. Polydactylous longitudinal erythronychia has also been observed as an idiopathic finding. Biopsy of the nail matrix and nail bed may be necessary to establish the diagnosis of a longitudinal erythronychia-associated condition. Indeed, a biopsy should be seriously considered in patients aged more than 50 years who present with a monodactylous longitudinal red band to exclude squamous cell carcinoma. Treatment of longitudinal erythronychia depends on the etiology. For patients with longitudinal erythronychia-associated discomfort or severe nail splitting, a surgical excision may provide not only the underlying diagnosis of the nail dyschromia, but also relief of related symptoms.     

Gene rearrangement studies in the diagnosis of primary systemic and nodular primary localized cutaneous amyloidosis

Difficulties may arise in the diagnosis of patients with clinical features suggestive of plasma cell dyscrasia-related amyloidosis (amyloidosis L), but without evidence of a paraprotein. We have employed gene rearrangement methodology to demonstrate the clonality of bone marrow cells not only in a patient with myeloma-associated systemic amyloidosis, but also in a patient with "primary" systemic amyloidosis without overt myeloma or a detectable paraprotein. Furthermore, we have shown the clonality of the amyloid-producing plasma cells within a skin nodule of a patient with primary localized cutaneous amyloidosis; by contrast, clonal rearrangement was not detected in bone marrow cells from this patient. This finding provides definitive proof that organ-limited nodular primary localized cutaneous amyloid deposits arise in relation to cutaneous plasmacytomas. Gene rearrangement studies may enable early diagnosis and initiation of treatment in patients with systemic amyloidosis L, as well as their differentiation from patients with organ-limited nodular cutaneous amyloidosis, who do not require aggressive therapy.     

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.     

Unusual cutaneous findings in primary systemic amyloidosis. Report of a case.

A case of primary, systemic amyloidosis is reported because of the unique location of cutaneous lesions. Amyloid deposits had occluded both external auditory canals. Both the cutaneous biopsies and postmortem examination established the diagnosis.     

Bullous poikilodermatitic amyloidosis of the skin with junctional bulla development in IgG light chain plasmacytoma of the lambda type. Histology, immunohistology and electron microscopy]

A 75-year-old patient presented with bullae, poilokilodermatic skin and nail dystrophy as signs of systemic amyloidosis 1 year before an IgG myeloma of the lambda type was diagnosed. The skin lesions appeared at mechanically irritated locations on the trunk and at the tensor sites of the extremities. Histology showed a subepidermal blister and necrotic keratinocytes in the epidermis. There were amyloid deposits in the papillary dermis perivascular, and in the deep dermis around eccrine glands and in arrectores pilorum muscles. Polyclonal antibodies allowed classification of the deposits as amyloid composed of lambda light-chain immunoglobulins. Electron microscopy revealed globoid deposits of non-branching filaments typical of amyloid. The blister was formed at the level of the lamina lucida, with the lamina densa at the base of the bottom of the bulla. So far, junctional blister formation in bullous amyloidosis of the skin has been described only once. Our case is the second report of this blister type, and to our knowledge the first published report of a junctional blister in myeloma-associated systemic amyloidosis.     

原发性系统性淀粉样变病1例

报告1例原发性系统性淀粉样变病。患者男，39岁。1年前肩关节突然出现酸痛，症状渐渐加重，双手掌皮肤发硬，肢体上抬及下蹲困难，舌不能外伸，吞咽时有梗阻感。曾经患有胸椎椎体骨髓瘤。皮肤科检查示面颈部、双侧腋下、腹部、阴茎、双大腿内侧泛发对称性的蜡样半球形丘疹，有融合，呈肤色或琥珀色。口腔黏膜肥厚，舌弥漫性浸润、质硬，呈巨舌。皮损组织病理检查示表皮萎缩，真皮与皮下组织淀粉样物质沉积，甲基紫染色阳性，诊断为原发性系统性淀粉样变病。给予泼尼松和雷公藤治疗，症状明显改善。     

Nails in systemic disease

Nail abnormalities secondary to systemic disease are important to the dermatologist because they are readily examined and may be the initial signal that systemic disease may be present. Some of the abnormal nail findings represent part of a symptom complex that may be useful in physical diagnosis. The knowledge of the correct onychopathologic etiology may give the patient the correct nail prognosis and may prevent institution of possible incorrect lengthy and costly treatment regimens. In this article, nail signs are grouped according to the characteristics of the change and according to systemic diseases producing signs.     

Primary, systemic amyloidosis and the dermatologist: where classic skin lesions may provide the clue for early diagnosis

Primary amyloidosis may present with skin lesions as a primary or sole expression of underlying plasma-cell dyscrasia. Classic skin lesions of primary, systemic amyloidosis are listed, and features suggestive of the diagnosis are discussed. Where this condition is considered in the dermatologist's differential, the investigations described may lead to an early diagnosis. When therapy can be initiated before the onset of organ failure, survival may be prolonged.     

Immunohistochemical staining properties of amyloids with anti-keratin antibodies using formalin-fixed, paraffin-embedded sections

Immunohistochemical staining properties of amyloids with anti-keratin antibodies were investigated using an avidin-biotin-peroxidase complex (ABC) system on formalin-fixed, paraffin-embedded sections. Anti-keratin antibody EAB-903 which recognize 66K and 57K daltons keratin peptides reacted with amyloid deposits in both lichen amyloidosus (LA) and macular amyloidosis (MA), but did not react with either primary systemic amyloidosis (AL), secondary systemic amyloidosis (AA) or heredofamilial amyloid polyneuropathy (AF). However, anti-keratin antibodies EAB-904 and MAK-6 did not react with any types of amyloids. These results suggested that immunohistochemical staining with anti-keratin antibody EAB-903 using formalin-fixed, paraffin-embedded sections appeared to be a useful method in making differential diagnosis of primary localized cutaneous amyloidosis (AD).     

“Retronychia – clinical and pathophysiological aspects”

Retronychia represents proximal ingrowth of the nail that occurs when the nail embeds backwards into the proximal nail fold. It is suspected when there is a persistent paronychia, particularly in the setting of trauma. Important clinical criteria for diagnosis are inflammation of the proximal nail fold, granulation tissue emerging from under the nail fold, thickening of the proximal portion of the nail plate and interruption of nail growth. The condition is rarely diagnosed and often misinterpreted, and is therefore unnecessarily treated with systemic antibiotics and antifungals. Avulsion of the nail confirms the diagnosis and it is the curative treatment. Conservative treatment with an adhesive technique is a valid option in early cases. We report 20 cases of retronychia diagnosed in our department between 2010 and 2013.     

Syndrome in Question

Immunoglobulin light chain amyloidosis is the most common acquired systemic amyloidosis. Its presentation is often insidious and progressive, which may delay diagnosis. The authors describe a rare case of immunoglobulin light chain amyloidosis in a 34-year-old man with scleroderma-like manifestation substantiated by multifarious laboratory investigations and the histopathologic feature of involved skin lesions stained with Congo red and crystal violet. This helps to maintain a high clinical suspicion of the disease when confronting similar skin presentation.     

Nodular cutaneous amyloidosis

A nodular cutaneous amyloidosis biopsy specimen from a solitary nodule of a 75-year-old patient was characterized by amino terminal sequence analysis and was proved to be derived from immunoglobulin kIII light chain. Five years after the diagnosis of amyloidosis in the skin was made, a rectal biopsy demonstrated amyloid deposits in a blood vessel. It is suggested that nodular cutaneous amyloidosis is a slowly progressive systemic disease of the AL type, that manifest itself mainly in the skin.     

Treatment of inflammatory nail disorders

This article provides an updated review on diagnosis and treatment of inflammatory nail disorders including psoriasis, lichen planus, trachyonychia, and autoimmune bullous disorders. Despite the significant negative repercussion of the nail psoriasis in the quality of life of patients, treatment is often not sufficiently effective. The efficacy of topical therapies is limited to nail bed psoriasis. Intralesional corticosteroid injections are extensively utilized in nail matrix psoriasis. Systemic immunosuppressant drugs such as methotrexate and cyclosporine have shown efficacy. Biologics, particularly infliximab and etanercept, have also demonstrated high efficacy in the treatment of severe nail disease. Nail matrix lichen planus can cause nail atrophy and irreversible nail scarring and requires prompt treatment with systemic steroids. There is not gold standard therapy for trachyonychia, but in most cases the nail signs improve spontaneously and treatment is not necessary. Nail changes in pemphigus and other autoimmune disorders respond promptly to systemic therapy with steroids and immunosuppressants.     

Macular amyloidosis associated with familial nail dystrophy

A case of macular cutaneous amyloidosis is described which was associated with autosomal dominant nail changes including subungual hyperkeratosis and discoloration. An unusual feature in this family was the resolution of the nail dystrophy during the third or fourth decade.