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Dermatomyositis and toxoplasmosis.

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taglandins on the cellular immune response is the
underlying cause of the chronic inflammatory reaction in MS.
Supported in part by Grants 1 PO1 CA 22507, CA 08748, CA
19267, CA 17404, and R 0 1 EY 01616, from the US Public
Health Service, National Institutes of Health.
During the course of this study, Dr Willoughby was recipient of an
Overseas Research Fellowship from the Medical Research Council
of New Zealand and a grant from the J. M. Foundation, New
Expert technical assistance was provided by Mrs M. Modi. We
thank Dr J. E. Pike of the Upjohn Company for his generous gift
of PGE, and PGE,.
1. Bourne NR, Lichtenstein LM, Melmon KL, et al: Modulation
of inflammation and immunity by cyclic AMP. Science
184:19-28, 1974
Bray MA, Gordon D, Morley J: Role of prostaglandins in reactions of cellular immunity. Br J Pharmacol 52:453P, 1974
Goodwin JS, Messner RP: Prostaglandin E inhibition of mitogen stimulation in patients with multiple sclerosis. Prostaglandlns 15:281-286, 1978
Gordon D, Bray MA, Morley J: Control of lymphokine secretion by prostaglandins. Nature 262:401-403. 1976
Kirby PJ, Morley J, Ponsford JR, et al: Defective PGE reactivity in leucocytes of multiple sclerosis patients. Prostaglandins
11:62 1-630, 1976
Offner H , Clausen J: Inhibition of lymphocyte response to
stimulants induced by unsaturated fatty acids and prostaglandins. Lancet 2:400-401, 1974
Offner H, Clausen J: Inhibition of lymphocyte response to
stimulants induced by unsaturated fatty acids and prostaglandins in multiple sclerosis. Lancet 2:1204-1205, 1974
Smith JW, Steiner AL, Parker CW: Human lymphocyte metabolism: effects of cyclic and non-cyclic nucleotides on stimulation by phytohemagglutinin. J Clin Invest 50:442-448, 197 1
Willoughby EW, Dupont B, Hansen J, et al: The indirect assay
for leucocyte migration inhibitory factor (LIFjstandardization
and the effect of pH. J lmmunol Methods 22:99-110, 1978
and Toxoplasmosis
G. F. M . Hendrickx, MD, J. Verhage, MD,
F. G. I. Jennekens, MD, and F. van Knapen, DVM
In a patient with childhood dermatomyositis, high
toxoplasrna antibodies were found at the time of diagnosis. A direct imrnunofluorescence technique demonstrated active toxoplasmosis in the muscle biopsy. The
response to treatment and follow-up in this patient
suggest that toxoplasmosis could have caused the dermatomyositis.
H e n d r i c k x GFM, Verhage J, Jennekens FGI, e t al:
Dermatomyositis and toxoplasmosis. A n n N e u r o l
5:393-395, 1979
A relationship between polymyositisldermatomyositis and toxoplasmosis has been suggested on the
basis of sequential antibody studies [ 4 , 5, 71. However, no parasite was seen in the biopsies of these
patients. In a case of childhood dermatomyositis
with high toxoplasma antibodies, we had the opportunity to study this relationship in more detail.
T h e eyelids o f a previously healthy 8-year-old boy became
swollen and red o v e r o n e week. D u r i n g t h e next nine
months, similar skin anomalies developed o n t h e hands,
elbows, a n d knees. His face became edematous. He developed fatigue and muscle weakness, and ultimately was
unable t o walk. Physical examination disclosed a heliotrope
erythema, most pronounced o n t h e eyelids, elbows, dorsal
surfaces of t h e hands, and t h e knees. I n s o m e of these
places t h e skin was flaky. Foci of vasculitis could be s e e n
around t h e nail matrices. T h e l o n g muscles of t h e back and
extremities w e r e weak; hypotonia was most pronounced in
t h e proximal muscle g r o u p s of t h e shoulder and t h e pelvic
The general laboratory findings w e r e normal. Slightly
elevated values w e r e obtained for creatine phosphokinase
( 6 1 U p e r liter, range 5 t o 45), and lactic dehydrogenase
( 4 8 7 U p e r liter, range 35 t o 189). T h e total hemolytic
c o m p l e m e n t (CH,,) and t h e s e r u m concentration of IgA,
I g G , and IgM w e r e normal. B y indirect immunofluorescence, s m o o t h and striated muscle autoantibodies and antinuclear antibodies w e r e n o t demonstrable. H i g h toxoplasma antibodies w e r e f o u n d in t h e s e r u m with both t h e
From t h e University Children’s Hospital Het Wilhelmina Kinderziekenhuis, Utrecht, and the Pathology Laboratory, Department of
Parasitology, National Institute of Public Health, Bilthoven. The
Accepted for publication, Sept 11, 1978.
Address reprint requests to Dr Hendrickx, Department of Pediatrics, Diaconessenhuis, Theodor Fliednerstraat 1, 5600 PD Eindhoven. The Netherlands.
0364-5134/79/040393-03$01.25 0 1978 by G. F. M. H e n d r i c k x 393
reciprocal IF titres
2043 4096
reciprocal CF titres
_ _ _ _ _ _o
- 32
- 16
- 8
- 4
- 2
indirect immunofluorescent antibody (IF) test and the comF i g I . Time-sequence study, i n relation to medication, of
plement fixation test (Fig 1). No specific IgM antibodies
toxoplasma antibodies-complement-fixation (CF) and imwere demonstrated. Inoculation of muscle material and
munojuorescence (IF) tests--in the serum of a patient with
liquor in mice did not reveal isolation of toxoplasma. T h e
childhood dermatomyositis.
electromyogram showed fibrillation potentials and positive
sharp waves. All motor unit potentials were polyphasic.
T h e interference pattern showed a slight reduction under
clinical recurrence developed, accompanied by contracmaximal volitional effort.
of the hip. Once daily, 2.5 mg of methotrexate was
The muscle biopsy showed enlargement of the perimyadded
for a short period to the prednisolone, but it was
sial spaces, which contained copious and often perivascusubsequently withdrawn because of ulcers in the mouth
lady localized cellular infiltrates. Inflammatory cells were
and skin lesions o n the face. About ten months after treatpresent in the walls of some of the small vessels. In some
ment was started, improvement occurred. From this time
places infiltrates composed of many lymphocytes, some
calcifications were radiographically visible in the soft
plasma cells, and large active histiocytes had spread betissues. During the administration of prednisolone alone o r
tween the muscle fibers in the fasciculi. Muscle fiber atin combination with methotrexate, the toxoplasma antirophy and changes such as loss of striation, vacuolization,
body titers rose again.
and phagocytosis were present in a predominantly perifascicular distribution. Free tachyzoites were seen in cryostat
sections from the muscle biopsy by a direct IF technique
using fluoresceinated high-titer rabbit antibody to ~ O X O - T h e p a t i e n t suffered from active toxoplasmosis as inplasma* [8](Fig 2).
dicated by the high antitoxoplasma titers, the decline
The diagnosis of dermatomyositis was made and the
of t h e s e titers under the influence of medication, and
child was treated with 2 mg per kilogram of prednisolone,
the p r e s e n c e of tachyzoites i n the muscle biopsy. I n
and with 25 mg of pyrimethamine once daily and 750 mg of
patients with a primary infection, I g M antibodies can
sulfadiazine four times daily to combat the toxoplasmosis.
be found in the blood over an initial period of several
Because thrombopenia developed, pyrimethamine and
months. T h e a b s e n c e of such antibodies in o u r pasulfadiazine were withheld after three weeks. Four weeks
suggests e i t h e r that t h e toxoplasmosis had b e e n
later the number of platelets was normal and the drugs
p r e s e n t for some t i m e or that reactivation had ocwere reinstated. Recurrence of thrombopenia led to a seccurred. Histological examination of t h e muscle biond cessation. These treatment procedures resulted in a
sharp reduction of antibody titers (see Fig 1). The compleopsy d i d n o t lead to identification of parasites, b u t
ment fixation test became negative, and the IF test
t h e direct immunofluorescence study with anshowed a residual titer of 1:512 in the spring of 1976.
titoxoplasma antiserum was successful in this respect.
The prednisolone was gradually reduced after two and a
The latter technique appears more sensitive.
half months. Four months after treatment was started a
The recent literature has suggested a relationship
between toxoplasmosis a n d polymyositis/derma+Commercially available from Wellcome, Beckenham, UK.
tomyositis [4, 5 , 71. In a c u t e toxoplasmosis, (focal)
394 Annals of Neurology
Vol 5 N o 4
April 1979
F i g 2 . Direct immunofluorescent staining of free toxoplasma
tachyzoites (arrows) in a cryostat section from the muscle
biopsy. The parasites are situated in loose connective tissue.
( ~ 8 0before
25 % reduction.)
tent toxoplasmosis seems to require concurrent or
previous treatment with antitoxoplasma agents.
1. Bohan A, Peter JB: Polymyositis and dermatomyositis. N Engl
myositis is described, but only rarely have parasites been seen in the muscle biopsies [6]. In our
case, coincidence between the simultaneous occurrence of toxoplasmosis and dermatomyositis cannot
be ruled out entirely. Etiology is always difficult to
demonstrate. There is only one previous description
of a case of polymyositis (with concurrent neurological abnormalities) in which the muscle biopsy
showed toxoplasma cysts without other changes [ 3 ] .
With respect to Kagen’s 141 hypothesis that patients with myositis might be predisposed, either by
the disease or by the therapy, to complications associated with toxoplasmosis, we can add that in our
patient the muscle biopsy showed tachyzoites before
therapy. The possibility that myositis can reactivate
latent toxoplasmosis cannot be excluded.
O n the basis of our findings, it appears advisable to
make a thorough search for active toxoplasmosis in
all patients with polymyositis/dermatomyositis. Investigation of muscle tissue for the parasite seems to
be important both in the choice of treatment and in
discovery of the pathogenesis of the diseases. If Toxoplasma gondii plays a role in the genesis of these
diseases, the current primary treatment with corticosteroids may have to be modified [l, 21. In the present state of our knowledge, high-dose prednisone
(prednisolone) in the presence of either active or la-
J Med 292:344-347, 403-407, 1975
2. Carpenter S, Karpati G, Rothman S, e t al: T h e childhood type
of dermatomyositis. Neurology (Minneap) 26952-962, 1976
3. Greenlee JE, Johnson WD Jr, Campa JF, e t al: Adult toxoplasmosis presenting as polymyositis and cerebellar ataxia. Ann
Intern Med 82:367-371, 1975
4. Kagen LJ, Kimball AC, Christian CL: Serologic evidence of
toxoplasmosis among patients with polymyositis. Am J Med
56:186-191, 1974
5. McNicholl B, Underhill D: Toxoplasmic polymyositis. Ir J Med
Sci 3:525-527, 1970
6 . Remington JS, Cavanaugh EN: Isolation of the encysted form
of Tnxnplasnza gondif from human skeletal muscle and brain. N
Engl J Med 273:1308-1310, 1965
7. Samuels BS, Rietschel RL: Polymyositis and toxoplasmosis.
JAMA 235:60-61, 1976
8. Van Knapen F, Panmabean SO: Identification of toxoplasma
infections in man and animal by a direct immunofluorescent
technique (in Dutch). Medikon 5:33-35, 1976
Case Report: Hendrickx et al: Dermatomyositis and Toxoplasmosis
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dermatomyositis, toxoplasmosis
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