426
Azathioprine 100 mg daily was added but soon withdrawn because of neutropenia. During the next month his disease flared and a mononeuritis multiplex affected the motor and sensory nerves in both legs and left hand. In addition he had a necrotising scleritis with a corneal melt in the right eye. He was referred to the Vasculitis Clinic at our hospital. Haemoglobin was 10-8 g/dl, WCC 18.1 x 109/1, ESR 90 mm/h, C-reactive protein (CRP) 110 mg/1 (normal < 10). Antineutrophil cytoplasmic antibodies (ANCA) titre was 320 with a cytoplasmic staining pattern. Radiography (cavitating lesions) and nasal mucosa biopsy (necrotising granulomatous vasculitic lesions) led to the diagnosis of WG. Intravenous cyclophosphamide with mesna, and intravenous methylprednisolone and oral prednisolone led to improvement, especially in the necrotising scleritis and neurological deficits. He was maintained on oral cyclophosphamide until thrombocytopenia occurred, and normal values returned after switching to intravenous cyclophosphamide. The cavitating pulmonary lesions resolved almost completely and he remained well for a year. The disease then flared. Despite six fortnightly pulses of cyclophosphamide 750-1000 mg, he became severely ill with widespread vasculitic lesions and the pulmonary nodules returned. He was given three 2 litre plasma exchanges, intravenous cyclophosphamide, doxorubicin and vincristine, and oral prednisolone, with no response to two courses. The cutaneous vasculitic lesions became widespread and were associated with pyrexia, arthralgia, scleritis, and sinusitis. ESR, CRP, and ANCA tests were abnormal. Oral etoposide 100 mg daily for 7 days every 3 weeks was started. Within a month gradual improvement was apparent and he has been in complete clinical remission on monthly courses of etoposide for a year with no adverse effects. Other approaches in WG, besides cyclophosphamide, include with intravenous plasmapharesis immunosuppressives, immunoglobulins,l and monoclonal antibodies against T-cell antigens,2 with varying degees of success. Etoposide3arrests DNA replication, apparently by inducing single-strand DNA breaks in the premitotic phase. It is most often used in combination regimens in small-cell lung cancers, testicular teratomas, and lymphomas. The main adverse effects include bone-marrow suppression with a leucocyte nadir after 15 days, nausea and vomiting, reversible alopecia, transient disturbances of liver function, and occasionally a mild peripheral neuropathy.4 D. D’CRUZ Lupus Arthritis Research Unit H. PAYNE and Department of Oncology, A. TIMOTHY St Thomas’s Hospital, London SE1 7EH, UK G. R. V. HUGHES Davies MJ, Fox CJV, Black CM, Lockwood CM. Treatment of systemic vasculitis with pooled intravenous immunoglobulin. Lancet 1991; 337: 1137. 2. Mathieson PW, Cobbold SP, Hale G, et al Monoclonal-antibody therapy in systemic vasculitis. N Engl J Med 1990; 323: 250-56. 3. Vogelsang NJ, Raghavan D, Kennedy BJ. VP-16-213 (Etoposide): the mandrake root from Issyk-Kul. Am J Med 1982, 72: 136-44. 4. Issell BF, Muggia FM, Carter SK, eds Etoposide (VP-16)—current status and new developments. New York: Academic Press, 1984. 1.
Jayne DRW,
Magnesium and chronic fatigue syndrome
who are deficient benefit from oral supplementation, although a few do also need intramuscular magnesium. We support the use of magnesium for CFS patients whenever there is a proven deficiency. In your May 30 note (p 1349), you correctly state the importance of recognising CFS patients with a major depressive illness. We believe that it is equally important to identify those with essential nutrient deficiencies. In our experience deficiencies of magnesium, vitamin Bl, and essential fatty acids are quite common. Correction is often accompanied by clinical improvement. You also say that alterations in muscle physiology are not seen in CFS patients. Although this is certainly true with many techniques that look at muscle contraction, one of us (J. M. H.) has previously reported changes in relaxation and resting indices with myothermography on patients with magnesium deficiency. We are finding a good correlation between this test and magnesium status in CFS patients. Improvements in the test results also parallel clinical improvement. BIOLAB Medical Unit, 9 Weymouth Street, London W1N 3FF, UK
JOHN MCLAREN HOWARD STEPHEN DAVIES ADRIAN HUNNISETT
J. Muscle action, trace elements and related nutrients the myothermogram In: Chazot G, Abdulla M, Arnaud P, eds. Current trends in trace element research. proceedings m international symposium on trace elements. Pans, 1987 London. Smith-Gordon, 1989: 79-85.
1. Howard
Detection of long-lasting antibody to hepatitis E virus in a US traveller to Pakistan SiR,—Most waterbome hepatitis due to infection with hepatitis (HEV) has occurred in developing countries, such as India, Pakistan, Burma, Algeria, Somalia, and Ethiopia.1 There have been E virus
isolated reports of HEV infection among travellers to India and Saudi Arabiaand in a traveller to Mexico.’ Here we report serological antibodies to HEV in a US traveller to Pakistan. A 54-year-old, previously healthy, well-nourished man developed malaise and jaundice on Jan 12, 1988, about 1 month after returning from Pakistan. There was no serological evidence for acute hepatitis due to hepatitis A or B virus, or to cytomegalovirus; non-A, non-B hepatitis (NANBH) was presumed. The patient had a hepatocellular involvement (aspartate aminotransferase [AST] 5000 IU, total bilirubin 10-7 mgfdl, direct bilirubin 7-2 mgldl, alkaline phosphatase 267 IU) which progressed to a cholestatic pattern (AST 387 IU, alanine aminotransferase 574 IU, total bilirubin 30 mg/dl, direct bilirubin 16-1mg/dl, alkaline phosphatase 196 IU). He was admitted for intravenous hydration and supportive care, and was discharged on Feb 21. The patient was readmitted 4 days later with persistent nausea and vomiting, despite treatment with prochlorperazine and metoclopramide, and progressive weight loss. He was started on peripheral hyperalimentation, but because of severe venous irritation from the catheter, tube feeding was initiated. Bilirubinand liver enzyme concentrations decreased and on March 4, the patient
discharged. July, 1991, a panel of twenty specimens from patients diagnosed with acute NANBH, including one from the patient was
In
SEROLOGICAL PROFILE OF PATIENT WITH SUSPECTED HEV EXPOSURE
SIR,-Dr Clague and colleagues (July 11, p 124) report normal status in 12 patients with chronic fatigue syndrome agree that magnesium deficiency is not the cause of CFS, but it is a factor in many of the patients we see. CFS patients, who are referred to us for nutrient status investigations by general practitioners and consultants from many centres, have often been investigated elsewhere. This preselection will skew our patient population, but we are nonetheless surprised that Clague et al did not find any magnesium deficiencies. In the investigation of several hundred CFS patients we have never seen 12 consecutive people with normal magnesium values. We use white cell magnesium and magnesium retention tests as well as
magnesium (CFS). We
measurement
of red-cell
magnesium
when necessary. That
Clague’s patients did not show any improvement in symptoms after intravenous magnesium should not be surprising since no patient was deficient in magnesium. We find that at least half the patients
*Recombinant antigens from Burmese (B) tltres
?o 300
are
positive
and Mexican
(M)stra of HEV Endpoint
Azathioprine 100 mg daily was added but soon withdrawn because of neutropenia. During the next month his disease flared and a mononeuritis multiplex affected the motor and sensory nerves in both legs and left hand. In addition he had a necrotising scleritis with a corneal melt in the right eye. He was referred to the Vasculitis Clinic at our hospital. Haemoglobin was 10-8 g/dl, WCC 18.1 x 109/1, ESR 90 mm/h, C-reactive protein (CRP) 110 mg/1 (normal < 10). Antineutrophil cytoplasmic antibodies (ANCA) titre was 320 with a cytoplasmic staining pattern. Radiography (cavitating lesions) and nasal mucosa biopsy (necrotising granulomatous vasculitic lesions) led to the diagnosis of WG. Intravenous cyclophosphamide with mesna, and intravenous methylprednisolone and oral prednisolone led to improvement, especially in the necrotising scleritis and neurological deficits. He was maintained on oral cyclophosphamide until thrombocytopenia occurred, and normal values returned after switching to intravenous cyclophosphamide. The cavitating pulmonary lesions resolved almost completely and he remained well for a year. The disease then flared. Despite six fortnightly pulses of cyclophosphamide 750-1000 mg, he became severely ill with widespread vasculitic lesions and the pulmonary nodules returned. He was given three 2 litre plasma exchanges, intravenous cyclophosphamide, doxorubicin and vincristine, and oral prednisolone, with no response to two courses. The cutaneous vasculitic lesions became widespread and were associated with pyrexia, arthralgia, scleritis, and sinusitis. ESR, CRP, and ANCA tests were abnormal. Oral etoposide 100 mg daily for 7 days every 3 weeks was started. Within a month gradual improvement was apparent and he has been in complete clinical remission on monthly courses of etoposide for a year with no adverse effects. Other approaches in WG, besides cyclophosphamide, include with intravenous plasmapharesis immunosuppressives, immunoglobulins,l and monoclonal antibodies against T-cell antigens,2 with varying degees of success. Etoposide3arrests DNA replication, apparently by inducing single-strand DNA breaks in the premitotic phase. It is most often used in combination regimens in small-cell lung cancers, testicular teratomas, and lymphomas. The main adverse effects include bone-marrow suppression with a leucocyte nadir after 15 days, nausea and vomiting, reversible alopecia, transient disturbances of liver function, and occasionally a mild peripheral neuropathy.4 D. D’CRUZ Lupus Arthritis Research Unit H. PAYNE and Department of Oncology, A. TIMOTHY St Thomas’s Hospital, London SE1 7EH, UK G. R. V. HUGHES Davies MJ, Fox CJV, Black CM, Lockwood CM. Treatment of systemic vasculitis with pooled intravenous immunoglobulin. Lancet 1991; 337: 1137. 2. Mathieson PW, Cobbold SP, Hale G, et al Monoclonal-antibody therapy in systemic vasculitis. N Engl J Med 1990; 323: 250-56. 3. Vogelsang NJ, Raghavan D, Kennedy BJ. VP-16-213 (Etoposide): the mandrake root from Issyk-Kul. Am J Med 1982, 72: 136-44. 4. Issell BF, Muggia FM, Carter SK, eds Etoposide (VP-16)—current status and new developments. New York: Academic Press, 1984. 1.
Jayne DRW,
Magnesium and chronic fatigue syndrome
who are deficient benefit from oral supplementation, although a few do also need intramuscular magnesium. We support the use of magnesium for CFS patients whenever there is a proven deficiency. In your May 30 note (p 1349), you correctly state the importance of recognising CFS patients with a major depressive illness. We believe that it is equally important to identify those with essential nutrient deficiencies. In our experience deficiencies of magnesium, vitamin Bl, and essential fatty acids are quite common. Correction is often accompanied by clinical improvement. You also say that alterations in muscle physiology are not seen in CFS patients. Although this is certainly true with many techniques that look at muscle contraction, one of us (J. M. H.) has previously reported changes in relaxation and resting indices with myothermography on patients with magnesium deficiency. We are finding a good correlation between this test and magnesium status in CFS patients. Improvements in the test results also parallel clinical improvement. BIOLAB Medical Unit, 9 Weymouth Street, London W1N 3FF, UK
JOHN MCLAREN HOWARD STEPHEN DAVIES ADRIAN HUNNISETT
J. Muscle action, trace elements and related nutrients the myothermogram In: Chazot G, Abdulla M, Arnaud P, eds. Current trends in trace element research. proceedings m international symposium on trace elements. Pans, 1987 London. Smith-Gordon, 1989: 79-85.
1. Howard
Detection of long-lasting antibody to hepatitis E virus in a US traveller to Pakistan SiR,—Most waterbome hepatitis due to infection with hepatitis (HEV) has occurred in developing countries, such as India, Pakistan, Burma, Algeria, Somalia, and Ethiopia.1 There have been E virus
isolated reports of HEV infection among travellers to India and Saudi Arabiaand in a traveller to Mexico.’ Here we report serological antibodies to HEV in a US traveller to Pakistan. A 54-year-old, previously healthy, well-nourished man developed malaise and jaundice on Jan 12, 1988, about 1 month after returning from Pakistan. There was no serological evidence for acute hepatitis due to hepatitis A or B virus, or to cytomegalovirus; non-A, non-B hepatitis (NANBH) was presumed. The patient had a hepatocellular involvement (aspartate aminotransferase [AST] 5000 IU, total bilirubin 10-7 mgfdl, direct bilirubin 7-2 mgldl, alkaline phosphatase 267 IU) which progressed to a cholestatic pattern (AST 387 IU, alanine aminotransferase 574 IU, total bilirubin 30 mg/dl, direct bilirubin 16-1mg/dl, alkaline phosphatase 196 IU). He was admitted for intravenous hydration and supportive care, and was discharged on Feb 21. The patient was readmitted 4 days later with persistent nausea and vomiting, despite treatment with prochlorperazine and metoclopramide, and progressive weight loss. He was started on peripheral hyperalimentation, but because of severe venous irritation from the catheter, tube feeding was initiated. Bilirubinand liver enzyme concentrations decreased and on March 4, the patient
discharged. July, 1991, a panel of twenty specimens from patients diagnosed with acute NANBH, including one from the patient was
In
SEROLOGICAL PROFILE OF PATIENT WITH SUSPECTED HEV EXPOSURE
SIR,-Dr Clague and colleagues (July 11, p 124) report normal status in 12 patients with chronic fatigue syndrome agree that magnesium deficiency is not the cause of CFS, but it is a factor in many of the patients we see. CFS patients, who are referred to us for nutrient status investigations by general practitioners and consultants from many centres, have often been investigated elsewhere. This preselection will skew our patient population, but we are nonetheless surprised that Clague et al did not find any magnesium deficiencies. In the investigation of several hundred CFS patients we have never seen 12 consecutive people with normal magnesium values. We use white cell magnesium and magnesium retention tests as well as
magnesium (CFS). We
measurement
of red-cell
magnesium
when necessary. That
Clague’s patients did not show any improvement in symptoms after intravenous magnesium should not be surprising since no patient was deficient in magnesium. We find that at least half the patients
*Recombinant antigens from Burmese (B) tltres
?o 300
are
positive
and Mexican
(M)stra of HEV Endpoint
