Sulphasalazine-Induced Systemic Lupus Erythematosus in a Patient with Ankylosing Spondylitis

Clinical Rheumatology -     

Ciprofloxacin-Induced Toxic Epidermal Necrolysis in a Patient with Systemic Lupus Erythematosus

Abstract. Toxic epidermal necrolysis (TEN), or Lyells syndrome, is a fulminant bullous dermatitis. TEN is often a drug-induced reaction and virtually any drug class appears capable of provoking it. We report here a case of TEN after administration of ciprofloxacin. Systemic lupus erythematosus (SLE) was suspected as a possible etiologic or modifying cofactor in TEN in this case.     

Strongyloidiasis Hyperinfection in a Patient with a History of Systemic Lupus Erythematosus

Strongyloidiasis is a parasitic disease caused by Strongyloides stercoralis, a nematode predominately endemic to tropical and subtropical regions, such as Southeast Asia. Autoinfection enables the organism to infect the host for extended periods. Symptoms, when present, are non-specific and may initially lead to misdiagnosis, particularly if the patient has additional co-morbid conditions. Immunosuppressive states place patients at risk for the Strongyloides hyperinfection syndrome (SHS), whereby the organism rapidly proliferates and disseminates within the host. Left untreated, SHS is commonly fatal. Unfortunately, the non-specific presentation of strongyloidiasis and the hyperinfection syndrome may lead to delays in diagnosis and treatment. We describe an unusual case of SHS in a 30-year-old man with a long-standing history of systemic lupus erythematosus who underwent a partial colectomy. The diagnosis was rendered on identification of numerous organisms during histologic examination of the colectomy specimen.Strongyloidiasis is an infection caused predominantly by the helminth Strongyloides stercoralis. This nematode is endemic to tropical and subtropical regions such as Southeast Asia, but is also present in more temperate climates, such as the northern United States and Canada.¹ Infection can rarely occur in areas thought to be non-endemic for the disease. Most chronically infected persons are asymptomatic. Clinical manifestations, when present, are usually mild and non-specific.²Immunosuppression places infected persons at risk for the Strongyloides hyperinfection syndrome (SHS), where the organism proliferates unchecked. This syndrome can cause exacerbation of the patient''s symptoms related to an increased parasite load in the intestine and lungs. Additional symptoms may arise as the organism involves organs not normally associated with the auto-infective life cycle.^2,3 We describe an unusual case of SHS in a patient undergoing chronic corticosteroid treatment for systemic lupus erythematosus (SLE). We review the literature regarding SLS in immunosuppressed patients, with emphasis on those with a history of SLE.A 30 year-old Hispanic man with an eight-year history of poorly controlled SLE came to an emergency department with fever, diffuse generalized pain, and bilateral upper and lower extremity edema. He was treated with antibiotics and methylprednisolone for presumed sepsis and lupus flare. The patient''s symptoms eventually resolved, but he was found to have nephrotic range protein and erythrocyte casts in his urine. He underwent an ultrasound-guided left renal biopsy, which later confirmed class IV G lupus nephritis. The next day, the patient''s systolic blood pressure decreased to 90 mm of Hg, and he began to experience diffuse abdominal pain, rebound tenderness, guarding, rigidity, and emesis. His leukocyte count and lactate dehydrogenase level were increased, and his hemoglobin level decreased significantly.Based on the clinical examination and findings of a computed tomographic (CT) angiography of the abdomen and pelvis (Figure 1), the patient underwent an emergent exploratory celiotomy. Blood clots were visualized in the peritoneal cavity, as well as active slow bleeding from the gastrocolic ligament and the base of the transverse mesocolon. Hematomata were identified in the omental bursa, pelvis, and hepatic flexure. No additional source of peritoneal bleeding was identified. The combined operative and CT findings suggested that the vascular supply to the distal transverse colon was compromised. An extended right hemicolectomy with a colonic mucous fistula and end ileostomy was performed.Open in a separate windowFigure 1.Computed tomographic (CT) image of the patient''s abdomen. Identified are a mesenteric hematoma with fluid density consistent with fresh blood (A), markedly edematous ascending and proximal transverse colon (B), perihepatic fluid consistent with old blood (C), and a defect in the posterior left kidney, consistent with biopsy site (D). There is no perinephric fluid or soft tissue changes to suggest acute hemorrhage of the renal biopsy site. There was no definitive CT evidence of acute vascular injury, pseudoaneurysm, contrast extravasation, perivascular contained hematoma, or dissection.Grossly, the serosa of the colon was covered by dark red-brown blood but was otherwise unremarkable. Several blood clots were seen within the mesentery and the omentum. The colonic mucosa was diffusely edematous with patches of yellow-tan exudate. There was a mild loss of the mucosal folds with focal edema. No lesion, ulceration, or perforation was identified. Microscopically, there were patchy areas of acute inflammatory cells and cellular debris overlying eroded mucosa. The lamina propria was markedly expanded by a lymphoplasmacytic infiltrate with scattered neutrophils and eosinophils.There were numerous filariform larvae and sharply pointed, curved tailed adult worms present within luminal acellular debris overlying the ulcerated mucosa. Similar organisms were seen in the lamina propria infiltrating into and running alongside intact crypts (Figure 2). Numerous organisms were seen in the lymphatics (Figure 3).Open in a separate windowFigure 2.Medium power view of colon, showing filariform larvae consistent with Strongyloides (arrowheads).Open in a separate windowFigure 3.High-power magnification of colon, showing a Strongyloides larva within a lymphatic space (arrowhead).Treatment of the patient''s Strongyloides hyperinfection was started with a 21-day course of ivermectin and albendazole. The patient then showed development of diffuse alveolar hemorrhage causing acute respiratory distress syndrome. A transbronchial lung biopsy was performed, which showed evidence of cytomegalovirus pneumonia, verified by immunohistochemical stainings. The lung biopsy specimen was remarkable for the presence of a giant cell granulomatous inflammatory response surrounding a filariform larva that presumably died secondary to the anti-helminthic agents (Figure 4). His cytomegalovirus pneumonia was treated with intravenous ganciclovir. His previously mentioned class IV lupus nephritis was treated with intravenous immunoglobulin and pulse steroids with steroid taper.Open in a separate windowFigure 4.High-power magnification of a lung biopsy specimen, showing filariform larvae consistent with Strongyloides (arrowhead).The resolution of his infection was confirmed with triplicate negative stool ova and parasites studies. Finally, on hospital day 60, he was discharged to a long-term rehabilitation facility. To date, he has no documented sequelae from his infection with Strongyloides.The interest in this case stems from histopathologic diagnosis of SHS in a patient without any relevant medical history. The patient''s medical history was remarkable only for SLE. The patient indicated a history of professional boxing, which may imply a history of extensive travel; however, this notion is speculative at best. The patient''s condition at admission closely mimicked symptoms described in the patient''s rheumatologic disorder. Accordingly, the index for suspicion for parasitic infections was low to non-existent. Were it not for the series of events that lead to the eventual histopathologic diagnosis, the patient likely would have experienced progression of the hyperinfection syndrome and eventual death.The life cycle of Strongyloides can either be an isolated free-living cycle where the helminth lives independently in soil, as well as a parasitic cycle in which the infective filariform larvae enter the host via intact skin, mature to adults, and proliferate. The rhabtidiform larvae created in the parasitic cycle are either passed in the stool or re-enter the circulation as filariform larvae by penetrating bowel mucosa or perianal skin to perpetuate the parasitic life cycle. This autoinfection cycle differentiates S. stercoralis from many other helminths,^1,4–6 and enables the organism to reside within the host for years, or even decades.Most persons infected with S. stercoralis are asymptomatic. Clinical manifestations, when present, are often mild and involve the intestine (abdominal pain, diarrhea, constipation, nausea, and weight loss), the skin (rash and pruritus, particularly at the site of entry of the larvae), and the lungs (cough, tracheal irritation, wheezing, and asthma).^2,3 The lack of specificity of the clinical syndrome, combined with a lack of sufficiently sensitive diagnostic tests, suggest that the current estimated prevalence of 3–100 million infected persons worldwide^1,4 is likely to be a significant underestimate.Immunosuppressive states place patients at risk for SHS. Although the diagnosis of hyperinfection is not clearly defined, it generally occurs when the immune status of the patient changes, and the organism proliferates unchecked and enters organs not normally involved in the worm''s normal intra-host life cycle. The patient may then show systemic manifestations, or more localized symptoms related to each organ the worm involves (e.g., meningitis or biliary obstruction). Invasion of the larvae through the bowel mucosa may also lead to secondary gram-negative septicemia as gut flora enter the blood stream in tandem with the larvae.^2,4,5 The patient may then undergo multi-organ dysfunction, septic shock, and die.A significant proportion of SHS cases are secondary to immunosuppressive drugs and primary immunodeficiency states, such as genetic disorders and hematologic malignancies. Of these contributing factors, corticosteroids are by far the most common precipitating agent.^4,7 The exact mechanism of this is unclear; hypotheses range from modulation of the T cell–mediated immune response to suppression of eosinophilia that normally occurs in response to parasitic infections.^3,8 Other hypotheses include a possible stimulatory effect of steroids on the adult female''s ability to produce eggs, or on the larval ability to mature.² Underlying infection with human T cell lymphotropic virus 1 may also affect the T helper immune response and predispose to disseminated strongyloidiasis, to the point where infection with human T cell lymphotropic virus 1 may be suspected if a patient exhibits sub-optimal response to anti-helminthic treatment.⁹ Interestingly, an association between acquired imunodeficiency syndrome and an increased risk of SHS has not yet been established. The reason for this finding remains unclear.^3,4,8There is no standard method of diagnosing strongyloidiasis. As in our case, histopathologic diagnosis may be rendered by direct visualization of the larvae or adult worms in biopsy specimens. The filariform larvae can be described histologically as a tubular esophagus measuring 180–380 μm in length with a blunted buccal end and notched tail.^1,10 Adult worms are considerably longer and are identified by one anterior esophagus and two posterior reproductive organs.¹¹ In intestinal biopsy specimens, these organisms are found in the crypt epithelium, the lamina propria, and submucosa.^6,11 Direct detection can also be made in stool specimens. However, some authors recommend analysis of multiple stool samples because a single stool examination may have sensitivity approximating 30%.^12,13 Examination of other specimens, such as sputum, duodenal aspirates, ascitic fluid, pleural fluid, peripheral blood smears, and cerebrospinal fluid, may be performed.^4,10 The blood agar plate method is a unique and sensitive diagnostic method in which presence of the organism is confirmed by visualizing tracts of bacterial colonies left in the organism''s wake as it travels across the agar plate''s surface.³ Newer modalities to detect Strongyloides-specific antigens have been described, such as polymerase chain reaction, which can simultaneously test for presence of other parasitic infections, but can show false-negative results because of potential polymerase chain reaction inhibitors present within patient samples or by inconsistent shedding of the organism in the feces.¹⁴The diagnosis of strongyloidiasis can also be made by using serologic analysis and identification of antibodies against Strongyloides. The enzyme-linked immunosorbent assay has been described as an effective method of testing because of its practicality, ability for automation, and its ability to detect the presence of antibody or antigen, depending on the assay.^14,15 Similar testing methods have been described; these include dipstick assays, gelatin particle agglutination, and immediate hypersensitivity skin tests to Strongyloides antigens.^3,15 Although reasonably effective, these types of tests are prone to cross-reactivity with other helminthic infections and are incapable of differentiating current from past infections.^4,14 Moreover, serologic assays may show false-negative results during acute infections or in immunosuppressed patients.^3,4,14,16 Assays or studies that directly detect the organism or its antigens may prove helpful in these cases. Luciferase immunoprecipitation system assays have recently been developed and showed promise in detection of Strongyloides-specific antibodies because of its high sensitivity and specificity, lack of cross-reactivity with other parasitic infections, and ability to monitor changes in antibody titers over time, resulting in an effective method of assessing treatment response.^14,16,17Treatment of uncomplicated cases requires standard treatment with anti-helminth drugs, such as ivermectin or albendazole. However, treatment protocols for SHS have not been well established because of lack of data. Furthermore, whether strongyloidiasis patients will benefit from concurrent reduction in immunosuppressive therapy remains debatable. Reports have generally advocated daily anti-helminthic treatment until stool ova and parasite samples are repeatedly negative for an extended period, often up to two weeks.^2,4 Response to anti-helminthic therapy is variable in immunosuppressed patients; accordingly, treatment in these patients depends on the etiology of the patient''s immunosuppression.³Thirteen other cases of SHS occurring in a patient with a history of SLE have been identified. For most of these cases, the diagnosis was either made too late in the disease course to prevent death,^18–22 or after the patient succumbed to disease.^8,23–25 In only four of these thirteen cases was the diagnosis made and treatment initiated sufficiently early to provide a favorable clinical outcome for the patient.^8,10,26,27 Compounding the issue is that these diagnoses were also reported in non-endemic areas, where index of suspicion is low,⁷ made possible because of the long periods that S. stercoralis can reside in a host. The high percentage of asymptomatic chronic strongyloidiasis, its non-specific symptoms and similarity in clinical presentation to entities such as the SLE flare (as in our patient), and its appearance in non-endemic areas contribute to the high mortality rate for SHS.⁵To prevent development of SHS and hyperinfection, screening for Strongyloides infection has been advocated for patients with a relevant medical history (such as residence or travel in disease-endemic areas) who are either in a immunosuppressed state or about to undergo immunosuppressive treatment.¹⁶ Serologic assays have been advocated as primary screening tests because of their reliability and the high sensitivity described in some assays.¹⁴ Although some assays are limited in their inability to differentiate current from past infection, some authors state that because of the persistence of strongyloidiasis, a patient with a compatible history and a positive serologic results may benefit from empiric treatment, such as a 1–2 day course of ivermectin if they are immunosuppressed or about to undergo immunosuppressive treatment.^3,16In our patient, the diagnosis was based on identification of an unusual load of worms and filariform larvae detected during the routine histologic examination of the colectomy specimen. A transbronchial pulmonary biopsy obtained soon thereafter isolated larvae in the alveolar septae. In our case, the rapid initiation of anti-helminthic therapy cleared his strongyloidiasis, verified by repeatedly negative stool ova and parasite samples. Our case underscores the importance of maintaining a baseline index of suspicion of stronygloidiasis in immunocompromised patients because this disease is potentially a fatal infection that can be treated successfully with anti-microbial agents.     

A Complex Case of Hepatitis in a Patient with Systemic Lupus Erythematosus

Liver involvement in patients with systemic lupus erythematosus (SLE) is considered rare. Previous treatment with potentially hepatotoxic drugs or viral hepatitis have usually been implicated as the main causes of liver disease in SLE patients. On the other hand, even after careful exclusion of these aetiologies, the problem remains whether to classify the patient as having a primary liver disease with associated autoimmune clinical and laboratory features resembling SLE, such as autoimmune hepatitis, or as having liver disease as a manifestation of SLE.  We report the case of an elderly woman who presented with acute hepatitis, who had been diagnosed with SLE 14 years ago and who also had Sjo¨gren’s syndrome and anti-phospholipid’s syndrome for several years. The histology depicted chronic active hepatitis and, after drug-induced hepatitis and viral hepatitis were excluded, the serological and clinical features were shown to be typical of liver damage caused by SLE. The patient was treated with azathioprine 100mg/d and prednisone 30 mg/d. The clinical symptoms resolved in 10 days and the laboratory values were normal at the end of the first month of therapy. Prednisone was progressively reduced, during a period of 4 months, to 10 mg/d but azathioprine was kept to the same dose. One year after the diagnoses the patient is still in remission.  Although uncommon, hepatic involvement is well recognised in SLE. The interest of this case lies in the differential diagnosis and recognition of this condition, which deserves an agressive treatment. Received: 8 March 1999 / Accepted: 8 March 1999     

Mesenteric Thrombosis Associated with Anticardiolipin Antibodies in a Patient with Systemic Lupus Erythematosus

A 45-yr-old female with mild chronic systemic lupus erythematosus for 20 yr, and with a stroke, digital infarction, and transient vocal cord paralysis during those 20 yr, had severe abdominal pain for 2 wk due to omental infarction associated with the presence of anticardiolipin antibodies. This report suggests that patients with otherwise mild systemic lupus erythematosus may develop severe recurrent thromboembolic events associated with anticardiolipin antibodies, that anticardiolipin antibodies may be associated with mesenteric ischemia, and that mesenteric ischemia associated with anticardiolipin antibodies should be considered in the differential of significant, unexplained abdominal pain in patients with systemic lupus erythematosus.     

Gastrointestinal Mucormycosis Mimicking Ischemic Colitis in a Patient With Systemic Lupus Erythematosus

This report describes the case of a 42-yr-old woman with systemic lupus erythematosus who presented with septic shock. Initially, a source of infection could not be found and the patient was started on stress dose corticosteriods and antibiotics. A CAT scan revealed thickened colon and endoscopy revealed possible ischemic colitis. She soon developed peritonitis, and was taken to surgery where gastrointestinal mucormycosis was found. The patient died despite amphotericin therapy.     

原发性胆汁性肝硬化合并系统性红斑狼疮的临床特点

目的观察和了解原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)合并系统性红斑狼疮(systemic lupus erythematosus,SLE)的临床特点。方法 2000年1月至2012年1月纳入北京协和医院风湿免疫科PBC数据库的PBC患者共322例,回顾性分析这些患者中合并SLE的临床特点;并与同期PBC数据库中未合并任何一种结缔组织病的PBC患者进行比较。结果 PBC合并SLE者共12例,占全部PBC患者的3.7%,均为女性,平均年龄(50.1±9.4)岁。12例PBC合并SLE患者中,9例为先出现SLE,3例为先出现PBC。PBC合并SLE组与单纯PBC组比较,白细胞计数、血红蛋白、血小板计数、碱性磷酸酶、γ谷氨酰转肽酶和IgM偏低,差异有统计学意义(P<0.05)。结论 PBC合并SLE患者并不少见,SLE的存在可能使PBC的肝损害相对变轻。     

系统性红斑狼疮生物疗药物浅谈

近年来,生物靶向治疗越来越多地应用于自身免疫性疾病患者的治疗,并取得了较好的疗效。系统性红斑狼疮(SLE)是一种多系统受累的自身免疫病,患者体内存在多种免疫紊乱。目前治疗SLE的生物制剂包括去除B细胞、抑制T-B细胞间相互作用以及拮抗炎性细胞因子和B细胞活化因子等方面的药物。本文简要介绍已经上市和正在进行临床试验的SLE生物靶向治疗药物。     

Vasculitis in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex heterogeneous autoimmune disease with a wide variety of clinical and serological manifestations that may affect any organ. Vasculitis prevalence in SLE is reported to be between 11 % and 36 %. A diverse clinical spectrum, due to inflammatory involvement of vessels of all sizes, is present. Even though cutaneous lesions, representing small vessel involvement, are the most frequent, medium and large vessel vasculitis may present with visceral affection, with life-threatening manifestations such as mesenteric vasculitis, pulmonary hemorrhage, or mononeuritis multiplex, with detrimental consequences. Early recognition and an appropriate treatment are crucial. Recent studies have shown that vasculitis in patients with SLE may present different clinical forms based on the organ involved and the size of the affected vessel. It is noteworthy that the episodes of vasculitis are not always accompanied by high disease activity. Recent articles on this topic have focused on new treatments for the control of vascular disease, such as biological therapies such as Rituximab and Belimumab, among others.     

Hypercalcaemia in Systemic Lupus Erythematosus

Hypercalcaemia is a common electrolyte abnormality. The vast majority of patients will be shown to have either hyperparathyroidism or malignancy. In less than 10% of patients other, less common causes of hypercalcaemia will be present. Systemic lupus erythematosus is a very rare cause of hypercalcaemia. It may be associated with lymphadenopathy and pleuritis to constitute a distinct clinical entity described as ‘hypercalcaemia–lymphoedema syndrome’. In these cases the pathophysiology of the hypercalcaemia is not completely understood. In some cases it is associated with elevated levels of parathyroid-related peptide (PTHrP). In others the level of PTHrP is normal, and it has been suggested that autoantibodies may cause hypercalcaemia by activating the PTH receptor. We describe a case of a woman who presented with severe hypercalcaemia, developed the hypercalcaemia–lymphodema syndrome and fulfilled the diagnostic criteria of systemic lupus erythematosus. Received: 30 April 2000 / Accepted: 8 November 2000