Association of a POEMS syndrome and light chain deposit disease: first case report.

Monoclonal immunoglobulin (Ig) deposition diseases are characterized by deposition in tissues of excessive amounts of the Ig, compromising organ functions. Light chain deposition disease (LCDD) and AL amyloidosis are the commonest [Buxbaum 1992]. LCDD is usually characterized by rapidly progressive renal failure with glomerular and tubular deposits of Ig fragments mostly composed by kappa light chain. Monoclonal Ig production can also be observed associated with various symptoms, that, taken together, have been described as the Crow-Fukase syndrome or POEMS syndrome. It associates polyneuropathy, organomegaly, endocrinopathy, monoclonal Ig, and skin changes. In POEMS syndrome, renal abnormalities are rare and are reported as a moderate renal insufficiency with mild proteinuria or acute functional renal insufficiency leading in some cases to end-stage renal failure [Fukatsu et al. 1991]. Although a monoclonal Ig is produced, no Ig deposit disease had been described in POEMS syndrome except a case of AL amyloidosis [Toyokuni et al. 1992]. Here, to our knowledge, we report the first case of an LCDD associated with a POEMS syndrome. Although an autologous bone marrow graft was realized, the monoclonal component reappeared and was responsible for end-stage renal disease, cachexia and death.     

Multiple myeloma presenting with widespread osteosclerotic lesions

Sclerotic lesions are rare in malignant monoclonal gammopathies, although they are occasionally associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes). In most cases, osseous lesions in POEMS syndrome present as an isolated sclerotic deposit or a combination of both lytic and sclerotic lesions. Diffuse osteosclerosis is extremely rare and may lead to the diagnosis of multiple myeloma, classically known to present as lytic lesions in the skeleton, with or without diffuse osteoporosis. We report a 74-year-old woman with widespread and substantial osteosclerotic lesions, associated with IgA-lambda myeloma, and with no other criteria for POEMS syndrome, and who was rapidly diagnosed with compression of the spinal cord. Detailed knowledge of imaging features in myeloma emphasises the need to consider plasma cell neoplasm in the differential diagnosis of any pattern of bone sclerosis. Although exceptional, multiple myeloma must be borne in mind in the presence of diffuse bone sclerosis.     

Serial renal biopsy findings in a case of POEMS syndrome with recurrent acute renal failure

This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case.     

Systemic capillary leak syndrome. Case report

We here report the case of a patient with systemic capillary leak syndrome (SCLS). This syndrome is a rare condition characterized by recurrent episodes of hypotension with hemoconcentration and hypoproteinemia. It is due to unexplained episodic capillary hyperpermeabilty that results in fluid and protein shift from the intravascular to the interstitial space: generalized edema, shock and renal failure follow. A 59 yo man was admitted to our intensive care unit because of unexplained shock with hemoconcentration, renal failure, and metabolic acidosis. Previous attemps to reverse shock in a medical ward with crystalloids and dopamine failed. An abdominal CT scan, a TEE, and chest X ray study were inconclusive. No sign or history of major infections or anaphylaxis were present. The patient was resuscitated with massive fluid infusions and norepinephrine on the guide of a Swan Ganz catheter. The diagnosis was made on the basis of a previous episode of severe shock complicated with renal failure and a compartment syndrome, the hemoconcentration, and the negative cardiopulmonary findings. A small amount of monoclonal immunoglobulin G, kappa chain, found in the serum confirmed the diagnosis. The SCLS should be considered in the differential diagnosis of idiopathic and anaphylactic shock. Patients may benefit from a prophylactic treatment with theophilline and terbutaline.     

Anaesthetic considerations in Castleman's disease

Castleman's disease is a lymphoreticular disorder, often localized and clinically silent. Systemic manifestations may occur. Castleman's disease may be associated with pathologies such as POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), AIDS, amyloidosis, pemphigus vulgaris, and other types of cancer such as lymphoma and Kaposi's sarcoma. Careful preoperative evaluation is required to determine whether associated mediastinal or spinal canal masses or haematological disorders are present. The significance of these pathologies for anaesthetic management is discussed. We present the case of a 27-year-old female patient with Castleman's disease (hyaline-vascular variant) requiring vaginal reconstruction due to recurrent sores and synechiae.     

Dense deposit disease in association with monoclonal gammopathy of unknown significance

Several renal pathologic entities have been reported in patientswith lymphoplasmacytic disorders with their typical excess immunoglobulinproduction. We report dense deposit disease in a patient whowas discovered to have an IgG kappa monoclonal protein withoutclinical evidence of underlying lymphoplasma cytic malignancyduring investigation for chronic renal failure with associatednephrotic range proteinuria. This case is unusual since densedeposit disease occurs only rarely in older patients and hasnot been reported in association with monoclonal gammopathyof unknown significance. Because of the diversity of renal lesionsassociated with lymphoplasmacytic disorders, renal biopsy isnecessary to assess the type of renal lesion in this patientpopulation.     

POEMS syndrome caused refractory ascites in a polycystic disease patient undergoing hemodialysis

A 60-year-old man with polycystic disease (PCD) undergoing hemodialysis was admitted to our hospital because of refractory ascites in September 2000. He had been diagnosed with probable chronic inflammatory demyelinating polyradiculopathy 6 months before admission. Though the ascites was bloody and exudative, the cytology was normal and cultures of bacteria and acid-fast bacillus were both negative. Hepatic venous outflow obstruction was excluded by several radiological examinations. Because of the presence of polyneuropathy, organomegaly, endocrine abnormality, M-protein, plasma cell dyscrasia, and skin lesions, POEMS, syndrome was diagnosed; this had caused the refractory ascites. Initial prednisolone therapy was effective for the refractory ascites, but it was not effective in preventing recurrence. He died due to cachexia in December 2000. This is a very rare case of the presence of both PCD and POEMS syndrome in a patient.     

Impairment of renal function in Schnitzler's syndrome

The list of multisystem diseases involving both kidney and skin is long and includes immunologic disorders like systemic lupus erythematodes, a broad variety of vasculitides, metabolic disorders like diabetes mellitus, and infectious diseases. The present work describes the first case of renal failure due to Schnitzler's syndrome, a rare entity characterized by the association of generalized chronic urticaria, monoclonal IgM gammopathy, and osteosclerotic lesions. The described patient experiences improvement of renal function after treatment with the chimeric anti-CD20 antibody rituximab, indicating that the impairment of renal function might be mediated by B-lymphocytes. Renal insufficiency is known to be a potential complication of hypocomplementemic urticarial vasculitis. The present case reveals that it can occur in normocomplementemic urticarial vasculitides as well. Schnitzler's syndrome is a rare but probably underdiagnosed syndrome. It should be considered in the differential diagnosis of rash and coincidental renal failure of unknown origin. Immunofixation of immunoglobulins constitutes the crucial diagnostic step, since monoclonal gammopathy is a constant clinical sign in this entity.     

A case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia associated with chronic renal failure

A rare case of idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) associated with chronic renal failure was described in this report. A 73-year-old male was admitted and diagnosed as IPL. IPL is proposed by Mori et al. in 1980. Clinical entity of IPL is (1) Polyclonal hyperimmunoglobulinemia (2) Systemic Lymphadenopathy characterized by remarkable mature plasmacytosis without atypism and by no destruction of the structures. (3) All disease with polyclonal hyperimmunoglobulinemia can be excluded. In this patient, physical findings showed enlarged lymph nodes (1-2 cm) in bilateral nuchal, submandibular, axillary and inguinal lesions. Laboratory examinations showed polyclonal hyperimmunoglobulinemia (especially IgG, IgA), anemia and renal dysfunction. Microscopic observation of hematoxylin-eosin staining in the axillary lymph node showed increased mature plasma cells without evidence of malignant growth. Immunoperoxidase staining showed intracytoplasmatic polyclonal immunoglobulins. IPL is known as invading other organs besides lymph node, for example skin, lung or kidney. This patient showed renal dysfunction (Cr clearance 11 ml/min, severe proteinuria). Nine cases of IPL and multicentric plasma cell type Giant Lymphnode Hyperplasia (GLH) concurrent with renal dysfunction were reported. Only in two of them chronic renal failure were reported. Twice a week hemodialysis improved his condition and laboratory findings.     

Cutaneous manifestations of paraproteinemia and their mechanisms

Disease entities characterized by the presence of paraproteins have a variety of cutaneous manifestations. These manifestations may be classified in the following categories as a function of their mechanisms: * extracutaneous deposition of paraproteins, as in amyloidosis * intravascular paraprotein deposition, as in cryoglobulinemia * cutaneous lesions resulting from the biologic activity of paraprotein, as in patients with normolipemic xanthoma with monoclonal immunoglobulin anti-LDL activity * abnormal cytokine secretion, as in AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndromes * unknown mechanisms.     

Renal involvement in POEMS syndrome

We describe a patient with POEMS syndrome whose renal biopsy specimen also showed nephropathy. Immunoelectron microscopy of the renal biopsy revealed the localization of immunoglobulin (IgA and lambda light chain) in the subendothelial space of the glomerular capillaries, a previously unrecognized finding. We conclude that the renal pathology in POEMS syndrome is unusual and distinct from microangiopathic glomerular involvement or idiopathic mesangiocapillary glomerulonephritis.     

Successful treatment of acute renal failure in a patient with essential mixed cryoglobulinemia using prednisolone and cryofiltration

We report a case of acute renal failure associated with cryoglobulinemic glomerulonephritis. The patient, a 49-year-old woman, was referred to our hospital because of acute nephritic syndrome. After admission, she developed oliguria, and hemodialysis was instituted. Renal biopsy was performed and the specimens showed moderate endocapillary proliferation, large deposits filling the capillary lumen ("intraluminal thrombi"), and a double-contoured appearance, which are typical morphologic features of cryoglobulinemic glomerulonephritis. Immunoelectrophoresis showed a monoclonal increase of IgM kappa. On the basis of these findings, we diagnosed type II essential mixed cryoglobulinemia. Cryofiltration was performed with oral administration of prednisolone. Following the start of therapy, the patient's renal function gradually improved. Because of severe hypoproteinemia, cryofiltration was discontinued after three sessions. However, renal function recovered and was maintained with prednisolone only. This case shows that acute oliguric renal failure caused by cryoglobulinemic glomerulonephritis can be reversible if immunosuppressive therapy, together with plasmapheresis in more severe cases, is instituted promptly.     

Acute renal failure in a young woman with Fisher-Evans' syndrome

A young female with Fisher-Evans' syndrome and a previous melanoma developed acute renal failure with generalized lymphoadenopathy and fever. The appearance of renal lesions is common in the course of several hematological disorders, but is unusual in Fisher-Evans' syndrome. Fisher-Evans' syndrome, defined as Coombs' positive hemolytic anemia and immune thrombocytopenia, is more frequently associated with the other autoimmune diseases, but not with renal involvement. In our case report, having excluded amyloidosis, myeloma, interstitial nephritis and sepsis, the rapid involvement of renal function with enlarged renal size seemed to suggest renal lymphoma. However, the lack of a monoclonal T-lymphocyte population in the renal tissue and peripheral blood, along with a clinical course characterized by a rapid reversibility of acute renal failure made this diagnosis rather an unlikely one. Polyclonal lymphocyte infiltration in a patient with a persistent autoimmune disease made us suspect a hyperimmune reaction. This syndrome is a non-neoplastic proliferation of B-cells involving an exaggeration of lymphocyte transformation. However, the clinical course is progressive and fatal, and can trigger a lymphoproliferative systemic disease. In our patient, two elements led us to suspect it was not a typical hyperimmune syndrome: first, polyclonal lymphocytes had massively infiltrated the kidney and, secondly, the clinical outcome was extremely favorable. Therefore, we were faced with an "atypical" and "singular" hyperimmune reaction with renal involvement, polyclonal proliferation of T-lymphocytes that had exhausted itself over time. Infective or toxic agents or drugs such as cyprofloxacin could have triggered the phenomenon, in the presence of a favorable condition such as Fisher-Evans' syndrome.     

Castleman's disease associated with myasthenia gravis

Castleman's disease presents as a peculiar type of lymph node hyperplasia. Traditionally, the disease has been classified on clinical grounds (solitary or multicentric) and by histologic appearance (hyaline vascular pattern, plasma cell predominance, or mixed lesions). It is now increasingly clear that there are different etiologies for each of these different subtypes. Reported associations include POEMS syndrome (polyneuropathy, organomegally, endocrinopathy, monoclonal gammopathy, and skin changes), paraneoplastic pemphigus, Hodgkin's disease, and follicular dendritic cell sarcoma. We present a case of Castleman's disease associated with myasthenia gravis, the third reported case in the literature. We discuss Castleman's disease and review the literature.     

Cast nephropathy in a case of Waldenström's macroglobulinemia

Waldenstr?m's macroglobulinemia is a low-grade lymphoplasmacytic lymphoma characterized by a circulating monoclonal IgM. The clinical manifestations are due to deposition of IgM in liver, spleen, and/or lymph nodes. Related symptoms include anemia and complications of the hyperviscosity syndrome. Renal involvement in classical cases of Waldenstr?m's macroglobulinemia is rare, and the pathological hallmark finding in the renal biopsy specimen is a thrombotic microangiopathy. We report the case of a 73-year-old female with the diagnosis of pernicious anemia for 2 years before she presented with acute renal failure. A renal biopsy performed suggested the diagnosis of myeloma cast nephropathy. However, bone marrow biopsy specimens and hematological studies did not support this diagnosis. Serum and urinary protein electrophoresis revealed a monoclonal lambda subtype IgM. Ultrasound imaging showed an enlarged spleen. The diagnosis of cast nephropathy in a patient with Waldenstr?m's macroglobulinemia was made. She underwent treatment with fludarabine and plasmapheresis/hemodialysis with dramatic improvement of her renal function.     

Normotensive scleroderma renal crisis: Case report and review of the literature

A 58 year old man presented with skin manifestations of scleroderma without systemic involvement. Within few weeks of oral corticosteroids and penicillamine therapy, rapidly progressive systemic sclerosis developed. The deterioration manifested by skin lesions, douse interstitial restrictive lung disease, acute renal failure with normal blood pressure values, and microangiopathic hemolytic anemia compatible with hemolytic uremic syndrome. Chronic renal failure developed and was treated by dialysis, but the patient died due to sepsis. The course of renal involvement was normotensive; antihypertensive therapy was not prescribed even once.

The association of scleroderma renal crisis with normal blood pressure is probably a rare and ominous combination.     

Nephrotic syndrome due to immunologically mediated hypocomplementic glomerulonephritis in a patient of Waldenström's macroglobulinemia

A 72-year-old man was diagnosed as having nephritic syndrome complicated by Waldenstr?m's macroglobulinemia (WM). A monoclonal IgM lambda protein and decreased serum complements were observed. The renal biopsy disclosed the capillary occluded by thrombi which was stained with IgG, IgA, IgM, C4, lambda light chain and slight kappa light chain in a granular pattern. Electron dense deposits were noted in the subendothelial spaces. An unusual case of WM who developed nephrotic syndrome due to immunologically mediated hypocomplementic glomerulonephritis is described.     

The spectrum of renal involvement in epidermolysis bullosa dystrophica hereditaria: report of two cases

Epidermolysis bullosa dystrophica Hallopeau-Siemens (EBDH) is one of the most severe inherited epidermolyses, a group of mechanobullous dermatological disorders. We observed two patients presenting with a severely multilating type of EBDH who developed biopsy-proven renal disease, which substantially altered the evolution and pathogenesis of their disease. In a boy, chronic postinfectious glomerulonephritis developed, most probably due to recurring superinfections of bullous skin lesions. He also experienced acute oliguric renal failure due to severe diarrhea during exacerbation of EBDH. A female patient developed a nephrotic syndrome due to secondary amyloidosis. Hypoalbuminemia caused further fluid losses through bullous skin lesions, aggravating intravascular hypovolemia and leading to rapid renal failure secondary to bilateral renal vein thrombosis. The study shows that, although rare, renal complications may alter the natural course of EBDH.     

Glomeruloid hemangioma. A distinctive cutaneous lesion of multicentric Castleman's disease associated with POEMS syndrome

A histologically distinctive cutaneous hemangioma occurring in two patients with biopsy-proven multicentric Castleman's disease associated with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome are reported. The lesions were multiple, and appeared as red to purple papules over the trunk and proximal limbs. Microscopically, ecstatic dermal vascular spaces were seen filled with aggregates of capillaries, resulting in structures reminiscent of renal glomeruli. Interspersed between the blood-filled capillary loops were plump "stromal" cells possessing clear vacuoles and periodic acid-schiff-positive eosinophilic globules. These cells had the immunohistochemical profile of endothelial cells (positivity for factor VIII-related antigen, and negativity for leukocyte common antigen, macrophage marker, and muscle-specific actin), and probably represented immature elements that had accumulated immunoglobulins and other proteinaceous material from the circulation. Because vascular lesions may appear before the full-blown POEMS syndrome develops, we suggest careful evaluation and follow-up of all patients presenting with glomeruloid hemangioma or cherry-type capillary hemangioma with focal glomeruloid features for potential development of this syndrome.     

Toxoplasmosis-associated hemophagocytic syndrome in renal transplantation

Toxoplasmosis is an infrequent, often difficult to diagnose and potentially lethal disease in kidney transplant recipients. Among reported cases, a few were associated with hemophagocytic syndrome (HPS), a rare condition characterized by widespread proliferation of macrophages phagocytizing blood elements, accompanied by fever and pancytopenia. We report here the case of a patient who received a Toxoplasma gondii positive kidney allograft and developed invasive toxoplasmosis 10 days after surgery, with high fever, skin rash, arthralgias, and renal failure, followed by pneumonia, anemia, thrombocytopenia, liver dysfunction, and encephalitis. Mislead by the absence of Toxoplasma on blood smears, alveolar fluid, renal graft biopsy, and negative brain computed tomography, confusion with serum sickness, and simultaneous herpetic infection, we failed to make the right diagnosis and the patient died with septic shock 11 days later. An HPS was revealed by a late bone marrow analysis. This may well be the fourth case ever reported of toxoplasmosis-associated HPS in renal transplant recipients.