LETTER TO THE EDITOR
The “HIV wasting syndrome” accounts for 14.6% of new AIDS cases per year,5 and is considered as indicative per se of full blown AIDS.’ The condition has been the subject of very little attention in the literature, and 4 of the 5 patients described in the only study devoted to the syndrome had received zid~vudine,~ a drug recently implicated at the origin of a mitochondria1 myopath^.',^ Indeed, evaluation of HIV wasting syndrome is problematic in developed countries where most patients with AIDS receive or have received zidovudine. In addition, occult self-therapy occurs in this context as demonstrated in a recent trial on zidovudine, in which the drug was detected in blood of 9% of patients receiving placebo.6 We evaluated, prospectively, 6 patients with the syndrome living in countries where zidovudine is not available. They were infected by HIV, (5 patients, Central African Republic) and HIV2 (1 patient, Senegal). All met the CDC criteria for the HIV wasting syndrome: major weight loss (>lo%), plus either chronic diarrhea (>30 days) or chronic weakness, and fever (>30 days), in the absence of concurrent illness other than HIV infection.’
Clinical findings (Table 1) included extreme fatigue, and marked amyotrophy involving proximal and distal segments of the limbs (circumferences of arms, 16.9 versus 26.3 cm in controls; thighs, 30.3 versus 52.8 cm; calfs, 23.7 versus 32.7 cm; P < 0.001). None of the patients complained of myalgias. All tendon reflexes were present. Opportunistic infections and neoplastic processes were not found. Biceps brachii muscle biopsy showed atrophy in all patients (atrophic factor: 180 to 590; n < loo’), that could be classified as diffuse nonselective atrophy (2 cases), grouped atrophy of both type I and I1 fibers suggestive of denervation (3 cases), and type I1 atrophy ( 1 case). Necrotic fibers were observed in 5 of 6 cases (0% to 14% of fibers, mean 4.8%),T-tubule dilatation in 4 of 6 cases, and mild perivascular inflammatory infiltrates in 3 of 6 cases. At electron microscopy, mitochondrial excess and myofilamentous changes such as cytoplasmic bodies, rod bodies and Z-disk streaming were not detected. Occasional mitochondria showed mild enlargement and some destruction of their cristae in 3 of 6 cases. The clinicopathological findings in our patients included major diffuse wasting that contrasted with a mild-to-moderate decrease of segmental muscle
Table 1. Clinical findings in 6 patients with HIV wasting syndrome. ~~
Case
Age/sex HIV (yrs) status
Staging of HIV Infection*
~~
~~
~
Weight Chronic Karnofsky loss Muscle diarrhea Chronic performance (%) weaknesst (stool/day) fever score
1 2 3
54/F 30/F 28/F
HIV, HIV, HIV,
IV A + IV B IV A I V A + IV B + IV C2
45 18 51
4 5 6
56/F 28/F 20/F
HIV, HIV, HIV,
IV A IV A IV A
47 38 49
++
+ +++ + + ++
-
No Yes Yes
40 70 30
12 7 6
Yes Yes Yes
40 40 30
8 4
Other features Sensory peripheral neuropathy Oral candidiasis, psychomotor slowing
f = female. ‘According to 1986 CDC cnferia. t+moderate, ++ marked, +++ severe
856
Letter to the Editor
MUSCLE & NERVE
July 1992
strength in most cases, and at muscle biopsy, diffuse or type I1 fiber atrophy, o r mild neurogenic features, as usually found in cachectic myopathy." Mild inflammatory infiltrates, which constitute a common infraclinical finding in the muscle of AIDS patients," were occasionally observed. Myalgias, mitochondria1 excess, and myofilamentous changes, previously described in zidovudine my~pathy,'.~were consistently absent. We conclude that the H I V wasting syndrome is a cachectic myopathy that differs clinically and pathologically from full-blown zidovudine myopathy. However, both conditions may be associated and, conceivably, it may be difficult to decide in practice whether muscle symptoms are drug-related or not when the typical clinicopathological findings of zidovudine myopathy are lacking. Laurent 881ec Department of Neuropathology Hdpital Henri Mondor, France, and Pasteur Institute of Bangui, Central African Republic Chokri Mhiri Department of Neuropathology Hdpital Henri Mondor, France Bernard Di Costanzo Department of Internal Medicine Centre National Hospitalier Universitaire de Bangui, Central African Republic Romain Gherardi Department of Neuropathology HGpital Henri Mondor, France
Letter to the Editor
1 . Brooke MH, Engel WK: The histographic analysis of human muscle biopsies with regard to fiber types. 2. Diseases of the upper and lower motor neurons. Neitrology 1969;19:378-393. 2. Dalakas MC, Illa I, Pezeshkpour GH, et al.: Mitochondria1 myopathy caused by long-term zidovudine therapy. ,\' EnglglJ M d 19!10;322: 1098- 1105. 3. Henson RA: Neurologic manifestations of paraneoplastic disorders, in Ashury AK, McKhann GM, McDonald WI (eds): Di.srusc of the N r t v o w Systrm. Philadelphia, Saunders, 1986, I>[> 1436- 1448. 4. Mhiri C, Baudrimont M , Bonne C;, et al: Zidovudine myopathy: a distinctive disorder associated with mitochondria1 dysfunction. Ann Neurol 1991;29:606-614. 5. Simpson DM,Bender AN, Farraye J. Mendelson SG, Wolfe DE: Human immunodeficiency virus wasting syndrome may represent a treatable myopathy. Neurology 1990;40:535538. 6. Volberding PA, Lagakos SW, Koch MA, et al: Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N EnglglJ hfed 1990;322:941-949. 7. World Health Organization: Acquired immunodeficiency syndrome (AIDS): 1987 revision of CDUWHO case definition for AIDS. Weekly Epiderniol Rec 1988;63:1-8.
MUSCLE & NERVE
July 1992
857
The “HIV wasting syndrome” accounts for 14.6% of new AIDS cases per year,5 and is considered as indicative per se of full blown AIDS.’ The condition has been the subject of very little attention in the literature, and 4 of the 5 patients described in the only study devoted to the syndrome had received zid~vudine,~ a drug recently implicated at the origin of a mitochondria1 myopath^.',^ Indeed, evaluation of HIV wasting syndrome is problematic in developed countries where most patients with AIDS receive or have received zidovudine. In addition, occult self-therapy occurs in this context as demonstrated in a recent trial on zidovudine, in which the drug was detected in blood of 9% of patients receiving placebo.6 We evaluated, prospectively, 6 patients with the syndrome living in countries where zidovudine is not available. They were infected by HIV, (5 patients, Central African Republic) and HIV2 (1 patient, Senegal). All met the CDC criteria for the HIV wasting syndrome: major weight loss (>lo%), plus either chronic diarrhea (>30 days) or chronic weakness, and fever (>30 days), in the absence of concurrent illness other than HIV infection.’
Clinical findings (Table 1) included extreme fatigue, and marked amyotrophy involving proximal and distal segments of the limbs (circumferences of arms, 16.9 versus 26.3 cm in controls; thighs, 30.3 versus 52.8 cm; calfs, 23.7 versus 32.7 cm; P < 0.001). None of the patients complained of myalgias. All tendon reflexes were present. Opportunistic infections and neoplastic processes were not found. Biceps brachii muscle biopsy showed atrophy in all patients (atrophic factor: 180 to 590; n < loo’), that could be classified as diffuse nonselective atrophy (2 cases), grouped atrophy of both type I and I1 fibers suggestive of denervation (3 cases), and type I1 atrophy ( 1 case). Necrotic fibers were observed in 5 of 6 cases (0% to 14% of fibers, mean 4.8%),T-tubule dilatation in 4 of 6 cases, and mild perivascular inflammatory infiltrates in 3 of 6 cases. At electron microscopy, mitochondrial excess and myofilamentous changes such as cytoplasmic bodies, rod bodies and Z-disk streaming were not detected. Occasional mitochondria showed mild enlargement and some destruction of their cristae in 3 of 6 cases. The clinicopathological findings in our patients included major diffuse wasting that contrasted with a mild-to-moderate decrease of segmental muscle
Table 1. Clinical findings in 6 patients with HIV wasting syndrome. ~~
Case
Age/sex HIV (yrs) status
Staging of HIV Infection*
~~
~~
~
Weight Chronic Karnofsky loss Muscle diarrhea Chronic performance (%) weaknesst (stool/day) fever score
1 2 3
54/F 30/F 28/F
HIV, HIV, HIV,
IV A + IV B IV A I V A + IV B + IV C2
45 18 51
4 5 6
56/F 28/F 20/F
HIV, HIV, HIV,
IV A IV A IV A
47 38 49
++
+ +++ + + ++
-
No Yes Yes
40 70 30
12 7 6
Yes Yes Yes
40 40 30
8 4
Other features Sensory peripheral neuropathy Oral candidiasis, psychomotor slowing
f = female. ‘According to 1986 CDC cnferia. t+moderate, ++ marked, +++ severe
856
Letter to the Editor
MUSCLE & NERVE
July 1992
strength in most cases, and at muscle biopsy, diffuse or type I1 fiber atrophy, o r mild neurogenic features, as usually found in cachectic myopathy." Mild inflammatory infiltrates, which constitute a common infraclinical finding in the muscle of AIDS patients," were occasionally observed. Myalgias, mitochondria1 excess, and myofilamentous changes, previously described in zidovudine my~pathy,'.~were consistently absent. We conclude that the H I V wasting syndrome is a cachectic myopathy that differs clinically and pathologically from full-blown zidovudine myopathy. However, both conditions may be associated and, conceivably, it may be difficult to decide in practice whether muscle symptoms are drug-related or not when the typical clinicopathological findings of zidovudine myopathy are lacking. Laurent 881ec Department of Neuropathology Hdpital Henri Mondor, France, and Pasteur Institute of Bangui, Central African Republic Chokri Mhiri Department of Neuropathology Hdpital Henri Mondor, France Bernard Di Costanzo Department of Internal Medicine Centre National Hospitalier Universitaire de Bangui, Central African Republic Romain Gherardi Department of Neuropathology HGpital Henri Mondor, France
Letter to the Editor
1 . Brooke MH, Engel WK: The histographic analysis of human muscle biopsies with regard to fiber types. 2. Diseases of the upper and lower motor neurons. Neitrology 1969;19:378-393. 2. Dalakas MC, Illa I, Pezeshkpour GH, et al.: Mitochondria1 myopathy caused by long-term zidovudine therapy. ,\' EnglglJ M d 19!10;322: 1098- 1105. 3. Henson RA: Neurologic manifestations of paraneoplastic disorders, in Ashury AK, McKhann GM, McDonald WI (eds): Di.srusc of the N r t v o w Systrm. Philadelphia, Saunders, 1986, I>[> 1436- 1448. 4. Mhiri C, Baudrimont M , Bonne C;, et al: Zidovudine myopathy: a distinctive disorder associated with mitochondria1 dysfunction. Ann Neurol 1991;29:606-614. 5. Simpson DM,Bender AN, Farraye J. Mendelson SG, Wolfe DE: Human immunodeficiency virus wasting syndrome may represent a treatable myopathy. Neurology 1990;40:535538. 6. Volberding PA, Lagakos SW, Koch MA, et al: Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. N EnglglJ hfed 1990;322:941-949. 7. World Health Organization: Acquired immunodeficiency syndrome (AIDS): 1987 revision of CDUWHO case definition for AIDS. Weekly Epiderniol Rec 1988;63:1-8.
MUSCLE & NERVE
July 1992
857
