A home-based approach to managing multi-drug resistant tuberculosis in Uganda: a case report

ABSTRACT: This case report describes an HIV-positive patient with recurrent tuberculosis in Uganda. After several failed courses of treatment, the patient was diagnosed with multi-drug resistant tuberculosis (MDR-TB). As adequate in-patient facilities were unavailable, we advised the patient to remain at home, and he received treatment at home via his family and a community nurse. The patient had a successful clearance of tuberculosis. This strategy of home-based care represents an important opportunity for treatment of patients in East Africa, where human resource constraints and inadequate hospital facilities exist for complex patients at high risk of infection to others.     

Fatal graft-versus-host disease following transfusion during open heart surgery

We report fatal transfusion-associated graft-versus-host disease (GVHD) in a patient who was not severely immunosuppressed. A 58-year-old man received 800 ml of fresh whole blood from his son and an unrelated volunteer donor during open heart surgery. On the 10th day after the operation, he suddenly had a high fever, followed by generalized skin rash and liver dysfunction. Pancytopenia due to bone marrow aplasia developed a week later. A skin biopsy revealed a cutaneous lesion highly compatible with acute GVHD. The patient did not respond to high-dose methylprednisolone therapy, and died of multiple organ failure on the 18th day after the operation.     

Case of Fusobacterium necrophorum sepsis (Lemierre's syndrome) with pulmonary septic emboli and liver abscess

The present article documents a case of Fusobacterium sepsis with a transient anticardiolipin antibody increase in an otherwise healthy 24-year-old patient. He was presented to the emergency room with headache and fever. His temperature was 39.5°C, laboratory results revealed a white blood count of 15.2×10(3)/μl and C reactive protein 22.6 mg/dl. The patient was admitted. Chest X-ray showed the infiltrate in bilateral lower lung area. He received 400 mg of clarithromycin per day. His all symptoms did not change. On the 8(th) day in the hospital, the patient's antibiotics were switched to pazufloxacin. Chest and abdominal CT scan showed some irregular patchy nodules of around 1 cm in diameter in the bilateral lower lung fields and a round low density lesion 3 cm in diameter in the right upper segment (S8) in the liver. Blood culture revealed Fusobacterium necrophorum. On the 10(th) day, the antibacterial agent was changed from pazufloxacin to ampicillin sulbactam. On the 17(th) day, we added clindamycin. As a result his temperature gradually returned to normal. It is reported that the titer of anticardiolipin antibody increases in the sepsis patients caused by Fusobacterium necrophorum. As his symptoms disappeared, his titer of anticardiolipin antibody also decreased. So we considered he had a transient anticardiolipin titer increase.     

Autoimmune hepatitis complicated by intolerable pain of lower extremities and shock due to azathioprine]

A 24-year-old woman was followed for about ten months with oral administration of prednisolone (22.5-35 mg/d) for autoimmune hepatitis. In June 1995, she noticed fatigue and appetite loss and blood chemistry revealed markedly deteriorated liver function. She was admitted to our hospital. The daily dose of prednisolone was increased to 60 mg. Her elevated levels of transaminases decreased gradually. Administration of azathioprine (100 mg/d) was started with tapering of prednisolone on August 18th. Ten days later, tender cervical lymphadenopathy and high fever occurred. Azathioprine administration was stopped immediately and intravenous antibiotics were given. On September 5th, 50 mg of azathioprine was administered again. Two hours later, the patient complained of intolerable pain from the lumbar region to the knee joints, which subsided following two injections of analgesics within a few hours. However, chills, high fever and hypotension (86/30 mmHg) subsequently developed. No bacterial growth was detected in blood culture. She was discharged on September 12th. On October 4th, she visited our out-patient clinic. The next day, she took one tablet (50 mg) of azathioprine at 10 o'clock. She noted intense pain from the thighs to the knees and calves around noon again. Her home doctor found that she exhibited shock (BP 67/?). She was immediately taken to our department. The same symptoms and signs as the above-mentioned occurred. Azathioprine was considered responsible for these two adverse reactions (shock) as an allergen. Later, systemic lupus eythematosus was diagnosed in 1996. And she died to pulmonary hypertension in May 1999. Physicians should be aware of the potential adverse effect of azathioprine administered in order to manage the patients with autoimmune disorders.     

Concurrent male gynecomastia and testicular hydrocele after imatinib mesylate treatment of a gastrointestinal stromal tumor

We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and noncommunicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST.     

A case of Beh?et's disease with esophageal ulcers complicated with systemic sclerosis, chronic hepatitis C, and pancytopenia]

A 62-year-old man was admitted to our hospital because of retrosternal burning pain and high fever in May, 2002. In 1995 chronic hepatitis C was diagnosed. Five years before admission he had been suffering from recurrent oral aphthous ulcers and genital ulcers. Distal scleroderma developed and the diagnosis of systemic sclerosis was made by skin biopsy in 1999. Prednisolone therapy, 5-30 mg/day, had been administered since then. In May 2000, he was referred to our department, and diagnosis of incomplete-type Beh?et's disease was made because he had erythema nodosa, oral aphthous ulcers and genital ulcers. Asymptomatic mild pancytopenia was also found. In November 2000, gastrofiberscopy revealed that he had esophageal and gastric ulcers resistant to regular treatment and was diagnosed as entero-Beh?et's disease, a subtype of the disease. The activity of esophageal and gastric ulcers was resistant to the low dose glucocorticoid and more than a moderate dose (30 mg/day) of prednisolone was necessary to reduce the activity. His gastrointestinal symptoms fluctuated with low dose prednisolone. Gastrofiberscopy on admission revealed that he had four shallow active oval ulcers in the middle-lower esophagus and distinct blind-fistula in the lower esophagus. Prednisolone were increased to 30 mg/day for his active entero-Beh?et's disease, however, his burning retrosternal pain remained. He died on the 81st hospital day due to severe pneumonia. This is a rare case of Beh?et's disease complicated with esophageal ulcers, systemic sclerosis, chronic hepatitis C, and pancytopenia. Of interest is the mechanism of coincidence of these diseases from the pathological point of view.     

A case of intravenous immunoglobulin-resistant Kawasaki disease treated with methotrexate

Kawasaki disease, an acute febrile vasculitis of unknown etiology, is usually treated with high doses of immunoglobulin (IVIG) and aspirin. However, 20% of children show persistent or recurrent fever despite IVIG, and coronary artery aneurysm progression. In such cases of resistance to IVIG treatment, repeated IVIG administration or the initiation of steroid therapy, and the use of cyclophosphamide have been reported. We aimed to show in this study that methotrexate (MTX) may be used as a treatment for Kawasaki disease resistant to IVIG treatment. We report the case of a 6-year old boy who was admitted at another hospital with an initial complaint of a fever for 5 days and skin rashes for 3 days. The patients fever persisted despite three courses of IVIG (2 gm/kg, 1 gm/kg, 1 gm/kg, respectively) over a 14-day period. On day 14 of his illness he showed a dilated right coronary artery, and on day 19 dexamethasone, at a daily dose of 0.3 mg/kg, was given but this resulted in defervescence. However, upon stopping the dexamethasone treatment, his fever recurred and he was transferred to our hospital. On days 31 and 38 of his illness, IVIG (400 mg/kg for 5 days, twice) was administered and from day 38 onwards the patient was given dexamethasone (0.6 mg/kg, daily) and MTX (10 mg/BSA, once weekly) whereupon his fever subsided and did not recur. On day 48 dexamethasone was replaced with prednisolone, which was subsequently tapered. The patient is now taking MTX and being observed on an outpatient basis. We report the case of a boy with IV-globulin resistant Kawasaki disease, who after repeated infusions of IVIG and steroid therapy showed fever recurrence, which that subsided after MTX treatment.     

A case of primary pyoderma-like aspergillosis occurring in a patient with a cervical spinal cord injury]

A 65-year-old man had tetraplegia caused by a cervical spinal cord injury, and could only lie in bed with a respirator. On the 14 th day of hospitalization, a rash developed on his back. The eruption grew rapidly, and became a giant erythematous plaque with ulcer, pustules, and red papules. Direct KOH examination showed branching Aspergillus hyphae. A slide culture showed subglobose shaped vesicles with phialides. Based on these findings, the case was diagnosed as primary pyoderma-like aspergillosis caused by Aspergillus fumigatus. He was treated with bifonazole and sulfadiazine silver, and one month later no Aspergillus hyphae were observed either by direct KOH examination or by culture. The patient died about 2 months later, however, because of aggravation of his general condition. Careful observation is necessary for compromised or unmoving patients with pyoderma-like aspergillosis.     

Hypersensitivity Pneumonitis Caused by Cephalosporins With Identical R1 Side Chains

Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient''s hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins.     

Pneumocystis pneumonia developed in two patients with rheumatoid arthritis during treatment of adalimumab

While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high-dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and β-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients.     

Hepatorenal syndrome: resolution of ascites by continuous renal replacement therapy in an alcoholic coinfected with hepatitis B, C, and human immunodeficiency viruses

A 39-yr-old male with hepatorenal syndrome type 1 and refractory ascites was treated with continuous renal replacement therapy (CRRT) resulting in clinical improvement. He was positive for antibodies to hepatitis B, C, and human immunodeficiency viruses, and had a history of chronic alcohol and iv drug abuse. The patient had 4 hospital admissions during a 12-wk period. He first presented with advanced liver disease including pedal edema and a serum ammonia level of 56 micromol/L (reference range: 11 - 35 micromol/L). In subsequent admissions, he had asterixis, nausea, vomiting, jaundice, and worsening pedal edema. On his 4th admission, there was lethargy, tense ascites, decreased urinary output, bilateral edema of the lower extremities and scrotum, serum creatinine of 6.2 mg/dl (reference range: 0.6 - 1.5 mg/dl), and weight gain of 16 kg during the prior 8 wk. During the first 3 hospitalizations, he was treated with lactulose with slight improvement. On the 4th admission, he was started on low-dose dopamine (3 microg/kg/min) and 25% salt-poor albumin without clinical improvement. A pulmonary artery catheter was placed and hemofiltration by CRRT was performed for 5 days, with removal of 26.7 L of fluid and a net reduction of 11 kg of body weight. Serum creatinine decreased to 4.2 mg/dl during CRRT and was 2.2 mg/dl at hospital discharge 2 weeks later. His PaO(2) improved from 66 to 78 mmHg and his systemic vascular resistance increased from 571 to 799 dyne.sec/cm(5). CRRT was effective in relieving severe fluid retention and producing marked clinical improvement. We suggest that CRRT should be considered for the treatment of refractory ascites including that caused by hepatorenal syndrome.     

Non-typhoid Salmonella meningitis complicated by a infarction of basal ganglia.

A previously healthy 16-month-old Korean girl with symptoms of fever, vomiting, and generalized tonic seizure was diagnosed to have Group D non-typhoid Salmonella meningitis. The patient was treated with ceftriaxone (100 mg/kg/day) and amikin (22.5 mg/kg/day) initially and ciprofloxacin (30 mg/kg/day) was added later because of clinical deterioration and disseminated intravascular coagulation. Brain CT performed on the second day showed a well-demarcated low density lesion in the right lentiform nucleus and both caudate nuclei, without evidence of increased intracranial pressure. MRI performed on the 11th day confirmed CT scan findings as well as right subdural fluid collection, brain atrophy, and ventriculomegaly. She underwent subdural drainage and later ventriculo-peritoneal shunt operation. Despite receiving intensive treatment, she still has severe neurologic sequelae. Our case shows that infarctions of basal ganglia and thalami are not specific for tuberculous meningitis and that meningitis complicated by infarction is indicative of grave prognosis.     

Chondrodysplasia punctata in an adult recognized as vitamin K antagonist embryopathy

A 32-year-old man with disproportionate short stature and striking facial dysmorphism came to genetic counseling as his wife was expecting their first child. In early infancy he had been diagnosed as having chondrodysplasia punctata, later regarded to be the autosomal dominant hereditary form. The expectant father was therefore convinced of a high risk of recurrence and vacillated between thoughts of taking his own life and of having his wife's pregnancy terminated. When his history revealed recurrent thromboses in his mother, treated with anticoagulants during pregnancy, her medical records of 1953 were located, and they disclosed that she had been treated with phenprocoumon (Marcoumar) from the 8th to the 12th and from the 13th to the 15th weeks of pregnancy. The patient has since become the father of a healthy son.     

Choroidal tuberculoma with membranous glomerulonephritis

We report treatment of a 24-year-old man with membranous glomerulonephritis (MGN) who developed a solitary choroidal tuberculoma in association with miliary tuberculosis during steroid therapy. In June 1995, the patient had developed nephrotic syndrome. He had refused renal biopsy at that time. So we treated him with corticosteroids having assumed a diagnosis of minimal change nephrotic syndrome. After initial corticosteroids and diuretics therapy for 5 months, his generalized edema resolved but proteinuria (3 positive) continued, suggesting the presence of other forms of glomerulonephritis. Renal biopsy performed in January 1996. The patient was diagnosed as having MGN. The patient was closely observed over a period of 34 months and remained stable without steroid therapy. However at 34 months, generalized edema was again noted and steroid therapy at high dosage was initiated. After 5 months of steroid therapy, he developed miliary tuberculosis and a solitary choroidal mass. An antituberculosis chemotherapeutic regimen was started and after a further 5 months, all clinical symptoms and signs of the pulmonary lesion were resolved and a measurable shrinking of the choroidal mass was recorded.     

A case of rheumatoid arthritis with acute lymphoblastic leukemia]

A 69-year-old male was diagnosed with rheumatoid arthritis(RA) in 1994. Good control of the RA activity had been obtained with sodium aurothiomalate (GST). However, polyarthritis reappeared in January 2003. He was examined at the Division of Rheumatology, Department of Internal Medicine, Saitama Social Insurance Hospital in August 2003. The treatment was switched from GST to salazosulfapyridine (SASP), with improvement of the polyarthritis. Subsequently, in March 2005, the patient developed fever, pancytopenia and liver dysfunction, and was admitted to Saitama Social Insurance Hospital. Since these abnormalities were suspected to be caused by SASP, this drug was stopped and prednisolone (PSL) was started at 10 mg/day. However, since the fever, pancytopenia and liver dysfunction persisted, bone marrow examination was performed and the patient was diagnosed with acute lymphoblastic leukemia (pre B cell type, L2). He was transferred to the Division of Hematology, Omiya Medical Center, Jichi Medical University, on 8(th) April, 2005 for induction chemotherapy. Although the induction therapy needed to be stopped because the patient developed dysphagia and biliary system dysfunction, complete remission (CR) was confirmed. It was difficult to restart chemotherapy in the patient because his general condition remained poor, with repeated episodes of aspiration pneumonia and newly detected stomach cancer. He was, therefore, transferred back to Saitama Social Insurance Hospital on 28(th) September, 2005. The ALL remained in CR and the RA activity had disappeared without therapy, but the patient died of pneumonia on 1(st) August, 2006.     

A case of vasculitis syndrome associated with bronchiolitis obliterans organizing pneumonia (BOOP)]

In 1996 36-year-old man was admitted into our hospital because of polyarthralgia, skin eruptions followed by multiple cutaneous ulcers, dry cough and elevation of C-reactive protein level. The finding of skin biopsy from left elbow was vasculitis. Chest CT showed linear interstitial shadow at bilateral dorsalis lungs. Transbronchial lung biopsy (TBLB) revealed marked infiltration of inflammatory cells in the bronchial walls and peripheral alveoli. In addition, eosinophils were not in branchoalveolar lavage (BAL) fluid. Moreover, video-assisted thoracic surgery (VATS) revealed organizing fibroblastic polyp and bronchiolitis obliterans at terminal bronchiole. We diagnosed his pneumonia as bronchiolitis obliterans organizing pneumonia (BOOP). Administration of oral prednisolone (40 mg/day) was begun and he experienced diminished BOOP and other clinical manifestations. Three years later he developed dry cough, dyspnea and digital ulcers again. Arterial blood gas analysis revealed marked hypoxemia and laboratory studies showed LDH (377 IU/ml) and CRP (8.27 mg/dl) levels were elevated. Chest CT pointed out an exacerbation of BOOP. Treatment with intravenous pulses methylprednisolone and oral prednisolone (60 mg/day) resulted in marked improvement of the clinical manifestations. We describe a rare case of vasculitis associated with BOOP.     

A case of trichophytia profunda acuta of the glabrous skin]

We report the case of a 68-year-old man with eruption on his left arm in the lesion where he wore his wrist watch. He was treated with topical steroid ointment at another clinic. He also suffered from tinea pedis. Examination of the scale and hair showed hyphal elements. Histopathological examination revealed granulomatous reaction around the hair follicles. We found no fungal elements in the tissue in spite of detecting serial sections of them. Trichophyton rubrum was cultured from tissue and scale, and the case was diagnosed as Trichophytia profunda acuta of the glabrous skin. Spontaneous remission was shown only by topical treatment for tinea pedis. A therapy of "wait and see" may be one choice.     

Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C.

We describe the case of a 56-year-old man who had high aminotransferase levels and anti-hepatitis C virus (HCV) antibodies. He underwent liver biopsy and biochemical screening to evaluate whether he would benefit from interferon (IFN) treatment. The patient was discharged with a diagnosis of HCV-related active chronic hepatitis, skin porphyria, and type 2 diabetes. On December 5, 1995, he began therapy with recombinant IFN-alpha at a dose of 3 MIU three times a week. He stopped this therapy in February 1996 because of asthenia, diplopia, headache, and anxiety. During IFN therapy, he had normal aminotransferase levels and no detectable HCV RNA, a condition that persists to the present. Between March and May 1996, the patient was admitted several times to a neurology clinic, where myasthenia gravis was diagnosed and treatment with pyridostigmine and cyclosporine was initiated. This case and others indicate that caution should be exercised in administering IFN because low doses can be correlated with myasthenia gravis in patients without malignancies.     

A case of slowly progressive type 1 diabetes mellitus developing myeloperoxidase-specific anti-neutrophil cytoplasmic antibody-associated vasculitis with hypertrophic pachymeningitis manifesting as multiple cranial nerve palsy

We report a 63-year-old man with a 35-year history of slowly progressive type 1 diabetes mellitus (SPIDDM), complicated with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis presenting alveolar hemorrhage and pachymeningitis. The patient was first diagnosed as having DM at age of 28 years old and deteriorated secretion of insulin and the typical clinical course led us to the diagnosis of SPIDDM. When he was 58 years old, he suffered from fever, headache, and alveolar hemorrhage. He was diagnosed as having MPO-ANCA associated vasculitis based on a high titer of MPO-ANCA and histological findings of lung biopsy. Treatment with steroid pulse therapy, followed by oral prednisolone and oral cyclophosohamide, resulted in clinical improvement. Five years later, he complained of double vision. A gadolinium-enhanced magnetic resonance imaging (MRI) study of the brain showed normal. Two months later, he developed right cranial nerve V~XII palsy. A second MRI study revealed thickening of the right temporal region and cerebellar dura mater, leading us to the diagnosis of hypertrophic pachymeningitis. He responded well to oral prednisolone (50 mg/day) and intravenous cyclophosohamide (500 mg). This is the first case report of SPIDDM complicated with MPO-ANCA-associated vasculitis, manifesting as alveolar hemorrhage and hypertrophic pachymeningitis.     

Genotype-4 hepatitis E in a human after ingesting roe deer meat in South Korea

The recent increase in the number of cases of indigenous hepatitis E virus (HEV) infection highlights the importance of identifying the transmission routes for the prevention of such infections. Presented herein is the first case of acute HEV infection after ingesting wild roe deer meat in South Korea. A 43-year-old male presented with abdominal discomfort and jaundice. He had not recently traveled abroad, but had eaten raw roe-deer meat 6-8 weeks before the presentation. On the 7th day of hospitalization the patient was diagnosed with acute viral hepatitis E. Phylogenetic analysis of his serum revealed genotype-4 HEV. This case supports the possibility of zoonotic transmission of HEV because the patient appears to have been infected with genotype-4 HEV after ingesting raw deer meat.