Acute pan-dysautonomia as well as central nervous system involvement and peripheral neuropathies in a patient with systemic lupus erythematosus

Abstract

A 32-year-old woman was diagnosed with leucopenia in 2002, being antinuclear antibody, anti-DNA antibody, and antiphospholipid antibody positive, and she was administered low-dose aspirin. In July 2006, she was admitted to our hospital because of pyrexia and abdominal pain. Examination revealed paralytic ileus, absence of the pupillary light reflex, dyshidrosis and anuresis. In addition, with high-level interleukin-6 in cerebrospinal fluid, the sensory nerve conduction velocity was derivation impotence. She was subsequently diagnosed with systemic lupus erythematosus (SLE) with central nervous system involvement, peripheral neuropathy as well as acute pan-dysautonomia. After pulse corticosteroid therapy, paralytic ileus was improved, however, the urination disorder persisted, and syncope due to orthostatic hypotension became marked. Plasma exchange and a second course of pulse corticosteroid therapy were performed, and were ineffective, whereas intravenous cyclophosphamide was effective. This patient is a rare case of central nervous system, peripheral neuropathy as well as acute pan-dysautonomia with SLE.     

A case of systemic lupus erythematosus (SLE) developing pan-dysautonomia]

A 43-year-old woman who had been diagnosed as primary Sj?gren's syndrome since 1986 developed severe constipation, urinary retention, dizziness at standing and polyarthralgia in February, 1990. Laboratory tests revealed proteinuria, hypocomplementemia and high titer of anti-DNA antibody. Diagnosis of SLE was made and she was admitted to our hospital on April 2, 1990. Physical examination on admission showed that she also had asymmetric pupils, impairment of sweating, orthostatic hypotension, neurogenic bladder, gastro-intestinal dysmotility and the diminution of R-R interval variability during deep breathing on the electrocardiogram. These findings suggested that she had pan-dysautonomia but there were no signs of motor and sensory disturbance. Because other diseases such as diabetes mellitus and amyloidosis which induced dysautonomia could be ruled out, her pan-dysautonomia seemed to be due to SLE. After the treatment with steroid pulse therapy, most of her dysautonomia improved rapidly. However, some of the disturbance had persisted for a long time. Pan-dysautonomia has been rarely reported as a complication of SLE, and high dose of steroid therapy at the early stage should be considered.     

Rapidly progressing central nervous system involvement despite of steroid pulse therapy in a case of systemic lupus erythematosus presented as mononeuritis multiplex

A 31‐year‐old‐woman with a 6‐month history of systemic lupus erythematosus (SLE) was admitted because of severe mononeuritis multiplex. Although she initially responded well with steroid pulse therapy, she developed unconsciousness again 3 weeks later just after a second course of steroid pulse. Laboratory evaluations revealed a high titre of anti‐DNA antibody, low complement levels, and positive lupus anticoagulant. She was treated with intravenous cyclophosphamide pulse therapy with immediate response. The clinical course of central nervous system involvement was very unusual for the response to steroid pulse therapy.     

Recurrent paralytic ileus associated with strongyloidiasis in a patient with systemic lupus erythematosus

We present an interesting case of recurrent paralytic ileus due to strongyloidiasis in a woman who was being treated with corticosteroids and immunosuppressants for systemic lupus erythematosus (SLE). She was also a carrier of human T-cell leukemia virus type I. She had a history of strongyloidiasis 8 years earlier. Recurrent episodes of paralytic ileus due to strongyloidiasis occurred during treatment of her SLE with corticosteroids. Ivermectin was given and improved the symptoms. This case shows that symptomatic strongyloidiasis can be induced in immunocompromised hosts by immunosuppressive therapy. It is important to rule out strongyloidiasis prior to starting immunosuppressive therapy in patients from endemic areas.     

A case of systemic lupus erythematosus (SLE) with a neurogenic bladder, successful treatment with intravenous cyclophosphamide pulse therapy]

A 46-year-old woman was diagnosed as having systemic lupus erythematosus (SLE) in 1990 and was treated with a daily maintenance dose of prednisolone (PSL). She suddenly developed urinary incontinence with a high grade fever and erythema of the arms and legs on May 10, 1998 and was admitted to our hospital. Laboratory findings on admission showed proteinuria, pancytopenia and hypocomplementemia. Anti-nuclear antibody, anti-DNA antibody and anti-Sm antibody were positive. Ultra-sonography after urination revealed dilatation of the bladder. Cystometrography showed an autonomous neurogenic bladder. The diagnosis of neurogenic bladder complicated by peripheral neurone disturbance associated with recurrence of SLE was made and intravenous methylprednisolone (m-PSL) pulse therapy (1000 mg/day) was initially administered for 3 days followed by 60 mg of daily per os PSL. Urinary incontinence did not improved. The same therapy was conducted 3 times with no response. Therefore, treatment was started with intravenous cyclophosphamide pulse therapy (500 mg/day) which resulted in marked improvement of urinary incontinence, hypocomplementemia, proteinuria and pancytopenia. This case developed a neurogenic bladder caused by lower neurone disturbance but did not show central nervous system lupus with upper neurone disturbance. Neurogenic bladder caused by lower neurone disturbance in SLE has rarely been reported. The vasculitis of SLE was probably responsible for this neuropathy and this case was successfully treated with intravenous cyclophosphamide pulse therapy.     

Kaposi's sarcoma in a patient with SLE

A 31-year-old woman with systemic lupus erythematosus (SLE) taking chronic corticosteroid therapy developed Kaposi's sarcoma. Three weeks after a single intravenous dose of cyclophosphamide for central nervous system vasculitis she died. Autopsy revealed disseminated Kaposi's sarcoma involving the skin and lung, as well as other visceral organs. This is the first case of widespread Kaposi's sarcoma developing in a patient with SLE.     

Early onset of paralytic ileus caused by simultaneous administration of bortezomib and azole antifungals in multiple myeloma patients

We herein report two patients (70- and 45-year-old men) with refractory multiple myeloma who developed paralytic ileus shortly after starting bortezomib therapy. Bortezomib (1.3 mg/m(2)) was given on days 1, 4, 8, and 11 with daily oral solution itraconazole or voriconazole. Twelve and 15 days after beginning the therapy, each patient developed paralytic ileus. Interestingly, no other signs of peripheral neuropathy such as fingertip numbness were observed at the onset of ileus. Sporadic cases of paralytic ileus after bortezomib therapy have been reported, most of which developed ileus after several courses of bortezomib therapy. Our cases developed paralytic ileus shortly after initiating bortezomib, strongly suggesting that autonomic neuropathy due to bortezomib was induced by the concomitant use of itraconazole or voriconazole.     

Reactive hemophagocytic syndrome in a case of systemic lupus erythematosus that was diagnosed by detection of hemophagocytosing macrophages in peripheral blood smears

A 38-year-old woman with pancytopenia and liver dysfunction was diagnosed with active systemic lupus erythematosus (SLE). On days 9 and 10 of admission, peripheral blood smears showed macrophages phagocytosing platelets, and reactive hemophagocytic syndrome (HPS) was diagnosed. Hemophagocytic syndrome was successfully treated with high-dose prednisolone therapy and one course of methylprednisolone pulse therapy. Detection of hemophagocytosing macrophages in peripheral blood smears would be a useful and noninvasive method of diagnosing SLE-associated HPS.     

Corticosteroid-resistant multiple colonic ulcers in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome effectively treated with intravenous cyclophosphamide pulse therapy

Abstract

We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus. Colonoscopy revealed multiple irregular and linear ulcers throughout the colon, which were resistant to corticosteroid pulse therapy and plasma exchange. The patient finally recovered after treatment with a relatively low dose of monthly intravenous cyclophosphamide (250?mg/m2) pulse therapy.     

Corticosteroid-resistant multiple colonic ulcers in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome effectively treated with intravenous cyclophosphamide pulse therapy

We report a rare case of a 17-year-old female with overlap syndrome (systemic lupus erythematosus and systemic sclerosis) who developed severe abdominal pain and bloody diarrhea accompanied by central nervous system lupus. Colonoscopy revealed multiple irregular and linear ulcers throughout the colon, which were resistant to corticosteroid pulse therapy and plasma exchange. The patient finally recovered after treatment with a relatively low dose of monthly intravenous cyclophosphamide (250mg/m²) pulse therapy.     

Acute central nervous system complications after pulse steroid therapy in patients with systemic lupus erythematosus

We describe 2 patients with systemic lupus erythematosus (SLE) who developed an acute psychosis and a cerebrovascular accident after pulse methylprednisolone therapy. A literature review revealed 8 additional patients with SLE with acute central nervous system complications after pulse therapy.     

A case of systemic lupus erythematosus complicated by alveolar hemorrhage and cytomegalovirus colitis

We report a rare case of systemic lupus erythematosus (SLE) complicated by alveolar hemorrhage and cytomegalovirus (CMV) colitis. Despite the successful treatment of lupus nephritis by steroid pulse therapy, the patient developed an acute alveolar hemorrhage 2 months later. Cyclophosphamide pulse therapy ameliorated the hemorrhage. One month later, she suddenly developed melena secondary to CMV colitis. Antiviral therapy was successful. We emphasize the importance of timely and precise differential diagnosis for successful management of complicated SLE.     

Overcoming treatment unresponsiveness mediated by P-glycoprotein overexpression on lymphocytes in refractory active systemic lupus erythematosus

P-glycoprotein (P-gp) expels various drugs from cells, resulting in multidrug resistance, including against glucocorticoids. Here, we present a case of systemic lupus erythematosus (SLE) that suggests the importance of initial intensive treatment in overcoming unresponsiveness due to P-gp overexpression on activated lymphocytes. A 28-year-old woman had been diagnosed with highly active SLE including severe pericarditis, hemolytic anemia, lupus nephritis, and retinopathy. The disease activity of SLE progressed despite 1mg/kg per day oral prednisolone. At the time, P-gp expression was extremely high, as evaluated by flow cytometric analysis on peripheral lymphocytes. After intensive treatment with three courses of methylprednisolone pulse therapy and plasmapheresis, we succeeded in controlling disease activity in association with marked reduction of P-gp overexpression; namely, the clinical symptoms immediately improved along with the reduction of P-gp expression. These results imply that patients with highly active SLE might have drug unresponsiveness that is mediated by P-gp overexpression on lymphocytes. Therefore, downregulation of P-gp by initial intensive immunosuppressive therapy might be important for overcoming glucocorticoid resistance. We also propose that measurement of P-gp on lymphocytes is a useful test for prediction of drug resistance and may assist in the selection of appropriate initial treatment.     

A case of lupus cystitis with a history of idiopathic thrombocytopenic purpura

A 36-year-old Japanese woman who had been diagnosed as having systemic lupus erythematosus (SLE) at the age of 34 began to complain of severe bowel symptoms and developed severe hydroureteronephrosis. She had a history of idiopathic thrombocytopenic purpura. Biopsy specimens from her bladder showed interstitial cystitis. She was diagnosed as having lupus cystitis, and treated with intravenous methylprednisolone pulse therapy followed by oral prednisolone and ureter catheterization. Her urinary and bowel symptoms were alleviated and the level of hydroureteronephrosis improved. We note that cystitis could be a primary manifestation of SLE. Patients not only with SLE but also with some autoimmune diseases require careful urological evaluation when they complain of severe bowel symptoms.     

Chronic inflammatory demyelinating polyradiculoneuropathy in a boy with systemic lupus erythematosus

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, autoimmune peripheral neuropathy. Systemic lupus erythematosus (SLE) is a multisystemic, autoimmune disease that can affect the central nervous system in about 40% of patients, with prevalence and incidence unknown in the pediatric population due to lack of multicenter studies. We report the case of a 13-year-old Mexican boy, diagnosed with CIDP at the onset of SLE, beginning with progressive muscle weakness of lower and upper limbs, without affection of the central nervous system. The patient had positive ANA, antiDNAdc, antiBeta2glycoprotein, anti-cardiolipin, ANCA-C and X. He received intravenous immunoglobulin, cyclophosphamide, steroids, and azathioprine and showed clinical improvement. It is important to take into account the presence of peripheral neurological disorders in patients with pediatric SLE, considering CIDP as an uncommon presentation, making the diagnosis important for better treatment and evolution.     

The association of −627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus

The objective of the study is to examine whether interleukin-10 (IL-10) promoter polymorphism is a marker of susceptibility of systemic lupus erythematosus (SLE) in Chinese patients in Taiwan. The study included 119 Chinese patients with SLE. One hundred unrelated healthy individuals living in central Taiwan served as control subjects. Each polymorphism was detected as a result of a polymerase chain reaction (PCR)-based restriction analysis. The PCR product length was determined to be 412 bp (CC) whereas two fragments of 236 and 176 bp were determined to be excisable lengths (AA). The relationship between the IL-10 gene polymorphism and clinical manifestations of SLE was evaluated. For the genotype and allelic frequency, there were statistically significant differences between the SLE patients and the normal control subjects (p=0.007 and 0.003, respectively). But we did not detect any association of carriage rate of the IL-10 polymorphism and the normal control subjects (p=0.077). Furthermore, we did not detect any association of IL-10 genotype with antinuclear antibody, malar rash, photosensitivity, discoid lupus, mucosal ulcer, arthritis, serositis, hematology, immunology, involvement of central nervous system, and renal disease involvement in the SLE patients. The significant relation of −627 IL-10 genotype and allelic frequency with SLE implies that the IL-10 gene polymorphism can serve as a candidate gene marker for further study in patients with SLE in Taiwan.     

Systemic lupus erythematosus in identical twins: a case report

In this report we describe the case of identical twin sisters that developed systemic lupus erythematosus (SLE). These patients have in common major histocompatibility complex class I and class II alleles and identical red blood cell antigens, which is a clear indication of monozygotic twins. Both twins showed high titers of anti-dsDNA antibody. However, only one of them manifested signs of lupus psychosis and was positive for the LE test, rheumatoid factor, anti-Scl 70, anti-SSA, and antiribosomal P antibodies. Both sisters lived together; therefore, the environmental factors were considered to be the same. Interestingly, these patients expressed different types of autoantibodies and the manifestation of disease was also quite different. When one of the twins was diagnosed with SLE, we began to closely follow up signs of the disease in the other twin periodically. This enabled us to promptly diagnose the second twin with SLE and she was successfully treated without progression of the disease. It is important to mention that following up the subsequent history of an identical twin diagnosed with SLE allowed early detection of the disease in the other twin.     

Asymptomatic pneumatosis cystoides intestinalis in a patient with systemic lupus erythematosus]

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of gas-filled cysts in the submucosa or subserosa of gastrointestinal tract. PCI has been widely recognized as a late manifestation of systemic sclerosis but seldom reported to take place in patients with systemic lupus erythematosus (SLE). We reported here a 13-year-old female who had been diagnosed to have SLE based on the following findings; malar rash, discoid erythema, proteinuria, positive antinuclear antibody and anti-DNA antibody. She had been treated with various immunosuppressive drugs including pulse use of corticosteroid, cyclophosphamide and cyclosporin A. She was referred to our hospital because of proteinuria and numbness on her right fifth toe, refractory to above treatment. On admission, the activity of her disease was already low and she had no abdominal symptoms. Plain X-ray film showed multiple round translucencies along the wall of the ascending and transverse colon. Colonoscopy revealed multiple firm-walled cysts distributing in the terminal ileum as well. A diagnosis of PCI was made and she was successfully treated with oral antibiotics and laxatives. The association of PCI with SLE is reviewed briefly.     

Catastrophic transverse myelitis in a patient with systemic lupus erythematosus

A 24-year-old Japanese woman was admitted to our hospital suffering from high fever and progressive paralysis in both legs. Magnetic resonance imaging of the spinal cord showed high-intensity signals from C5 to Th4 and from Th7 to L1 on T2-weighted images. The patient was diagnosed as having acute transverse myelitis , which was a complication of systemic lupus erythematosus based on the serological findings. Despite aggressive immunosuppressive treatments including corticosteroid pulse therapy, plasmapheresis, and intravenous cyclophosphamide, the paralysis of her lower extremities did not improve. In the catastrophic type of lupus-associated TM, which develops extensively and longitudinally along the spinal cord, the prognosis still seems to be poor despite intensive treatments.     

Nine-year's follow up on the appearance of autoantibodies in a child with idiopathic thrombocytopenic purpura subsequently developing lupus with central nervous system manifestations]

We describe a 23-year-old female who developed SLE 9 years after asymptomatic idiopathic thrombocytopenic purpura (ITP) with positive antinuclear antibody (ANA). Although the platelet count was normal before the onset of SLE, the titer of ANA was gradually increased and also autoantibodies, including antibodies to SS-A/Ro, single-stranded DNA (ss-DNA) and nuclear ribonucleoprotein (RNP) changed to positive. At 23 years of age, the patient was admitted to our hospital because of fever, butterfly rash and polyarthritis. Anti double-strand DNA (ds-DNA) antibody and anti Smith antigen (Sm) antibody were positive and the platelet count and titer of complements were decreased. The patient was diagnosed as SLE and treated with 60 mg/day of prednisolone. Despite steroid therapy, psychiatric symptoms appeared. Additional treatments with steroid pulse therapy and double filtration plasmaphresis resulted in the improvement of SLE including the central nervous system manifestations. This case suggested that increased titer of ANA and the appearance of antibodies to SS-A, ss-DNA, RNP, ds-DNA and Sm in ITP patients predict the development of SLE. Routine checkup of autoantibodies is needed to manage ITP with positive ANA.