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Cardiac amyloidosis mimicking hypertrophic cardiomyopathy.

Amyloid infiltration of the heart may frequently masquerade as other cardiac disorders. The extended use of echocardiography may contribute to an erroneous diagnosis of hypertrophic cardiomyopathy, as both conditions show several features in common. This was the case with the patient reported below. A low QRS amplitude, an increased right ventricular wall thickness, thickened cardiac valves, and a pericardial effusion may, however, indicate amyloid infiltration. The diagnosis of systemic amyloidosis of immunocytic origin was subsequently established in our patient. A definitive diagnosis of amyloid heart disease requires endomyocardial biopsy, but it is suggested that typical noninvasive findings together with demonstration of amyloid in an organ other than the heart is sufficient for a reliable diagnosis. In addition, systemic manifestations may contribute to a correct diagnosis in generalized amyloidosis. Our patient had features consistent with the rare muscle pseudohypertrophy syndrome, which is associated with immunocytic amyloidosis.

Amyloidosis↗

Poikiloderma-like cutaneous amyloidosis in an ethnic Chinese girl.

Primary cutaneous amyloidosis is the deposition of amyloid in the skin without involvement of internal organs. It is easily diagnosed when presented in its typical manifestation. Atypical or rare clinical presentations can pose diagnostic difficulties. Poikiloderma-like cutaneous amyloidosis (PCA), a rare variant of primary cutaneous amyloidosis, was first reported in the literature in 1936 (1). It is characterised by: 1) poikilodermatous skin lesions; 2) lichenoid papules; 3) cutaneous amyloid deposit in the pigmented and lichenoid lesions; 4) light sensitivity; 5) short stature; and 6) other features such as blister formation or palmoplantar keratosis. Ogino coined the term PCA syndrome when these unusual features present early in life (2). We report a 26-year-old Chinese woman who presented with poikilodermatous skin lesions and was misdiagnosed as poikiloderma atrophica vasculare (PAV) on the basis of clinical appearance without any histological proof. The diagnosis of PCA was made after skin biopsy which showed amyloid deposits in the skin. This condition can easily be confused with other true poikiloderma skin diseases. Histology is important in confirming the diagnosis.

Adult↗

Familial amyloidosis cutis dyschromica: six cases from three families.

Amyloidosis cutis dyschromica, a rare form of primary cutaneous amyloidosis requiring histopathological confirmation, is characterized by generalized, asymptomatic hyperpigmentation intermingled with several hypopigmented spots without papulation, atrophy, and telangiectasia. Its onset usually begins before puberty. We describe six patients from three families, four male and two female. The mean age at onset was 10.2 years. Although the skin eruptions had developed extensively since childhood, systemic involvement was not evident even after long-term follow-up. Due to its unique and characteristic features, this condition should be considered as a separate entity and differentiated from other variants of primary cutaneous amyloidosis. The familial occurrence in our report suggests a genetic causal factor in this disease.

Adolescent↗

Immunohistochemical demonstration of amyloid P component in skin of normal subjects and patients with cutaneous amyloidosis.

The presence of amyloid P component (AP) in dermal deposits of cutaneous amyloidosis was demonstrated by a direct immunofluorescence technique using an antibody to serum amyloid P component (SAP). AP was also shown, for the first time, to be a constituent of normal human skin. It was present at the periphery of dermal elastic tissue fibres, in basement membranes of dermal blood vessels and surrounding eccrine sweat glands but was absent from the dermo-epidermal basement membrane. The staining pattern in cutaneous amyloidosis was morphologically distinctive and readily distinguishable from staining of thickened vascular basement membranes in porphyria. Immunofluorescence with anti-SAP is simple and specific and may become the procedure of choice in the differential diagnosis of amyloidosis.

Amyloid↗

Lichenoid skin lesions as a sign of beta 2-microglobulin-induced amyloidosis in a long-term haemodialysis patient.

We report a case of beta 2-microglobulin-induced amyloidosis. The patient was a 40-year-old man suffering from non-amyloid nephropathy, who had been treated by haemodialysis for 20 years. Lichenoid skin lesions, consisting of groups of pin-head-sized shiny papules, were present on the arms and trunk. On histological examination, amyloid deposits were present, principally in the dermal papillae, but also around the sweat ducts and hair follicles. The amyloid displayed potassium-permanganate-resistant Congo red affinity, and green birefringence under polarized light. Immunohistochemically, beta 2-microglobulin was demonstrated in the lesions, confirming that they were a manifestation of beta 2-microglobulin-associated amyloidosis. Skin lesions of this type have not been reported previously in beta 2-microglobulin-associated amyloidosis.

Adult↗

Discoid lupus erythematosus with secondary amyloidosis.

BACKGROUND: Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes. OBJECTIVES: To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples. METHODS: Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid. RESULTS: Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample. CONCLUSIONS: Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.

Amyloid↗

High-dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study.

Amyloid light chain (AL) amyloidosis is the result of a clonal plasma cell expansion, in which monoclonal light chains transform to amyloid deposit in various tissues and can lead to organ dysfunction and organ failure. The median survival of patients with AL amyloidosis without therapy is 10-14 months. With high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT), haematological and clinical remission rates of up to 50% of treated patients have been reported from phase II studies. HDM followed by ASCT appears to prolong survival in patients, if haematological remission can be reached. In this phase II study, we evaluated vincristine, adriamycin and dexamethasone (VAD) as induction chemotherapy prior to stem cell mobilization and HDM with ASCT. The regimen was, in general, feasible in patients with AL amyloidosis, but VAD chemotherapy had a considerable World Health Organization (WHO) grade III-IV toxicity (25%) and mortality (7%) rate. VAD pretreatment did not interfere with stem cell mobilization and HDM with ASCT was possible in 86% of patients. The overall treatment efficacy was comparable with reported results of HDM and ASCT without preceding chemotherapy. We could not show an additional benefit of VAD induction in terms of increasing haematological response rate; however the 13% mortality rate after HDM and ASCT in our series was lower than the previous report.

Adult↗

Studies in vivo and in vitro of serum amyloid P component in normals and in a patient with AA amyloidosis.

Pure serum amyloid P component (SAP) was isolated from a normal donor pool, from individuals with the different genotypes of an MspI restriction fragment length polymorphism (RFLP) linked to the SAP gene, and from a patient with AA amyloidosis. The SAP preparations were all identical and all behaved as a single homogeneous species in polyacrylamide gel electrophoresis, isoelectric focussing, reverse-phase chromatography, binding in vitro to phosphoethanolamine-Sepharose (binding constant 2.4 x 10(7) l/mol) and AL amyloid fibrils (1.6 x 10(8) l/mol), and binding to amyloid deposits in vivo in mice with casein-induced amyloidosis. The in vivo metabolism of 125I-SAP from a single donor was normal and identical in three healthy individuals representing the three different MspI RFLP genotypes. There is thus no frequent polymorphism of SAP in normal subjects, and SAP altered with respect to the characteristics studied here is not a necessary condition for pathogenesis of systemic AA amyloidosis.

Amyloidosis↗

Treatment of experimental murine amyloidosis with dimethyl sulfoxide.

Dimethyl sulfoxide was administered intravenously for 60 days to twenty mice with casein-induced amyloidosis. Partial or total disappearance of amyloid deposits occurred in all treated animals. The urine of these animals contained a substance from which amyloid fibrils could be synthesized. A control group of mice with casein-induced amyloidosis given saline injections showed massive amyloid deposition in the liver and in the spleen at the end of the experiment. Neither the urine of these mice nor the urine of normal control mice treated with dimethyl sulfoxide contained substances from which amyloid fibrils could be synthesized. It is our assumption that dimethyl sulfoxide treatment of mice with amyloidosis resulted in a break up of amyloid fibres into small subunits which were excreted in the urine.

Amyloid↗

Spontaneous major bleeding in acquired factor X deficiency secondary to AL-amyloidosis.

Abnormal bleeding may be seen in up to a third of patients with amyloidosis. Factor X deficiency is the commonest acquired coagulopathy in amyloidosis. While mild intracutaneous bleeding is common, spontaneous life-threatening haemorrhage is rare. We report a case of acquired FX deficiency due to amyloid light chain (AL)-amyloidosis presenting with spontaneous retroperitoneal bleeding. The diagnostic and management issues in this patient are discussed.

Aged↗

Microscopical atrial amyloidosis in chronic heart disease.

Nineteen out of 121 consecutive cardiac biopsies from 107 patients were found to contain amyloid deposits on routine Congo red screening. Seventeen were left atrial appendages removed during mitral valvotomy for chronic rheumatic mitral valve disease while the remaining two were right atrial appendages excised during surgical repair of atrial septal defects. The distribution of amyloid deposits within the atria and their tinctorial characteristics are described. The high prevalence of atrial amyloidosis observed could not be attributed to generalized or senile amyloidosis. The possibility that this is a distinctive localized form of amyloidosis secondary to chronic heart disease is discussed.

Adolescent↗

Dystrophic amyloidosis: a local complication of tissue damage with heterogeneous distribution.

Seventeen consecutive patients with dystrophic amyloidosis are reported here (eight Chinese, three Indian, three Iban, two Malay and one Caucasian). Ten were females and seven males, with ages ranging from 12 to 80 years (mean of 48 years). Five instances of dystrophic amyloidosis occurred in areas of tissue damage in the cardiovascular system, including fibrotic cardiac valves and an atheromatous plaque. Three occurred in osteoarthritic joint tissue. Of note were three occurrences in endometriotic cyst walls, four in the fibrotic walls of epidermal cysts, one in a hernial sac and one at the edge of a skin ulcer. All deposits were congophilic and exhibited green-birefringence and permanganate-resistance. Immunohistochemistry did not reveal reactivity for AA protein or immunoglobulin lambda or kappa light-chains. AP protein was detected in 35% of cases. Our results show that, besides the usual sites of osteoarthritic joints and damaged heart valves, dystrophic amyloidosis can complicate other areas of chronic tissue damage and fibrosis such as walls of cysts and ulcers. While the pathogenesis and biochemical nature remain unresolved, immunohistochemistry indicates that neither AA nor AL proteins are present in the deposits, and suggests that a different amyloid protein is involved.

Adolescent↗

Spontaneous resolution of acquired factor X deficiency in amyloidosis.

We describe the case of a 51-year-old man with systemic amyloidosis in whom factor X activity was initially 6% of the normal. Amyloidosis was responsible for congestive heart failure and a nephrotic syndrome but there was no bleeding diathesis. A 12-month trial of melphalan and prednisone failed to improve cardiac and renal dysfunction; factor X levels remained low. Eighteen months after this treatment was stopped, factor X spontaneously normalized although renal insufficiency persisted. We suggest that the possibility of a spontaneous factor X recovery must be considered when evaluating efficacy of therapeutic agents in amyloidosis.

Amyloidosis↗

Senile cardiac amyloidosis: evidence of two different amyloid substances in the ageing heart.

In a material of seventy-two persons over 70 years of age, forty-seven cases of amyloidosis of the heart were found. In thirty-nine cases, deposits occurred only in the atria (isolated artrial amyloidosis, IAA), while in eight cases amyloid also was seen in the ventricles (senile cardiac amyloidosis, SCA). In some of the latter cases, small amyloid deposits occurred in other organs, especially the lungs. Some definite differences existed between the amyloid substance in SCA and IAA. Thus, tryptophan was demonstrated histochemically in SCA but not in IAA, and, furthermore, amyloid fibrils isolated from patients with IAA lacked protein Asca, the fibril subunit protein of senile cardiac amyloid. It is concluded that the ageing heart may be the target of two different forms of amyloid, one only affecting the atria, while the other is more widespread within the heart and sometimes also is found in other organs.

Aged↗

Changes in natural killer activities in experimental secondary amyloidosis.

Natural killer (NK) cell activity in experimental murine amyloidosis was studied. In CBA/J mice, which show a high incidence of amyloidosis, NK activity was significantly decreased after 1 week of casein treatment. In C3H mice, which show a low incidence of amyloidosis, NK activity was not changed by casein treatment. Pretreatment with lipopolysaccharide in vivo enhanced the NK activities in CBA/J and C3H mice. These increases were not observed after casein treatment. The lowered NK activity of cells from CBA/J mice after casein treatment was restored to the normal range by indomethacine in vitro. Depletion of adherent cells from the spleen cells treated with casein had no effect on NK activity. Single-cell assay showed that casein treatment impaired the killing but not the binding of NK cells to target cells. After casein treatment, the splenic serum amyloid A (SAA) level gradually increased in CBA/J mice but remained low in C3H mice. NK activity was suppressed by the addition of serum obtained from CBA/J mice treated with casein but not by normal control serum. And partially purified AA protein obtained from the spleen of CBA/J mice treated with casein also suppressed NK activity in vitro.

Amyloid↗

Familial lichen amyloidosis.

In Japan, two cases of familial lichen amyloidosis were found in a mother and her son, who had a history of cutaneous amyloidosis in 11 adults of three family generations. HLA types in both patients were rather common ones among Japanese people. Topical application of dimethyl sulfoxide was effective in the mother but not in the son. Familial cutaneous amyloidosis (FCA) is a rare disease in Japan although nonfamilial-type is not uncommon. Possible parameters of FCA are discussed. The author recommends using "FCA" without "primary" as the name of the disease.

Adult↗

Thermosensitive lichen amyloidosis.

BACKGROUND: A 26-year-old male presented with a 3-year history of lichen amyloidosis. On examination, there was a pigmented papular eruption with a ripple pattern affecting the limbs and trunk but sparing the axillae, antecubital and popliteal fossae, central chest, neck and face. There was also prominent sparing of the skin overlying the superficial veins of the limbs. The sparing of the superficial veins of the limbs by lichen amyloidosis raised the possible role of cutaneous temperature in governing the distribution of amyloid deposits in our patient. OBSERVATIONS: Total body infrared thermography demonstrated consistent sparing of the amyloid deposits in areas with higher cutaneous temperatures such as the neck and axillae as well as the course of the superficial veins. The cooler areas such as the extensor surfaces of the arms and legs corresponded to areas of amyloid deposition. Narrow band ultraviolet B (NBUVB) phototherapy over a 5-month period resulted in a marked improvement of pruritus and clearing of the amyloid deposits. CONCLUSIONS: Our patient clearly demonstrated lichen amyloidosis in a thermosensitive distribution. This may be a gross manifestation of previous reports of in vitro thermosensitivity of amyloid fibril formation and may have potential implications in treatment at least in a subset of patients demonstrating this clinical feature.

Adult↗

Urticaria, arthralgia, and nephropathy without amyloidosis: another variant of the Muckle-Wells syndrome?

The term Muckle-Wells syndrome (MWS) describes an autosomal dominant disorder characterised by various combinations of urticaria, sensorineural deafness, amyloidosis, arthralgia and skeletal abnormalities. We describe a family with nephropathy and several symptoms of MWS, but no evidence of deafness or amyloidosis. Since nephropathy without amyloidosis has never been reported in MWS, but deafness is a feature of all reported pedigrees, we conclude that members of this family have a previously unreported inherited predisposition to urticaria, arthralgia and nephropathy which is distinct from the MWS phenotype.

Adolescent↗