TRICHINOSIS: CLINICAL REPORT AND HISTOCHEMISTRY OF MUSCLE

Brian Gross, MD, and J o d Ochoa, MD, PhD

Abstract: A 35-year-old woman contracted severe trichi- nosis which was atypical in that it lacked a gastroin- testinal prodrome and periorbital edema, and in that eosinophilia developed only late in the course of the illness. The patient developed an incapacitating myo- sitis as well as complications of encephalopathy, myo- carditis, and retinal hemorrhages, resulting in severe debilitation of more than two and onehalf months' du- ration. Muscle histochemistry illustrated previously un- reported features.

MUSCLE & NERVE 2:394-398 1979

Trichinosis is a parasitic infestation which only rarely comes to contemporary clinical attention, most cases being clinically inapparent.3 Sympto- matic patients often have a prodrome character- ized by abdominal cramping and diarrhea, fol- lowed by myalgias, fever, periorbital edema, and eosinophilia. The syndrome rarely lasts longer than six weeks. We report a case of a lady who pre- sented in an atypical fashion, and whose illness was unusually prolonged and accompanied by the rare complication of retinal hemorrhages. A muscle bi- opsy obtained early in the course of' the disease established the diagnosis and provided insights into the enzyme histochemistry of muscle fibers and parasites.

CASEREPORT

A 35-year-old mother sampled partially cooked pork as she prepared an Oriental meal in early May of 1977. Approximately one week later, she noted calf and thigh pain which, over the next two

weeks, also involved her neck, back, arm, respira- tory, and ocular musculature. She denied fever, chills, nausea, diarrhea, vomiting, or abdominal cramping. She noted a subtle change in perception of auditory and visual images as well as some im- pairment of thought processes, but she denied fo- cal weakness, paresthesias, diplopia, scotomas, tin- nitus, or vertigo. Family members who subsequently ate the cooked meal did not develop similar s yrn p toms.

Physical examination on admission, May 2 1 , 1977, revealed an ill-appearing white female with a blood pressure of 100/50, a pulse of 110, and an oral temperature of 37.8"C. ?40 petechiae or per- iorbital edema were noted. She had pain on lateral gaze and slight ptosis bilaterally. There were no conjunctival or scleral hemorrhages; pupils were equal, round, and reactive; and visual fields were full. Multiple flame-shaped retinal hemorrhages were present bilaterally but lacked vitreous exten- sion. Venous pulsations were present. The neck was supple and the lungs were clear. Cardiac ex- amination revealed a dynamic precordium, a grade I N 1 systolic ejection rniirmur along the left sternal border, an S-4 gallop, and no pericardial friction rub. Abdorriinal and pelvic examinations were un- remarkable, and stool was guaiac negat.ive. Severe

From the Dartrnouth-Hitchcock Medical Center Department of Neurology Hanover NH

Acknowledgments This study was supported by a grant from the Mus cular Dystrophy Association The histochemistry was performed by E J Boogusch

Address reprint requests to Dr Ochoa at the Department ot Neurology Dartmouth-Hitchcock Medical Center, Hanover NH 03755

Received for publication November 16 1978 accepted for publication December 5. 1978

01 48-639XM20510394 $00 0010 1979 Houghton Mifflin Professional Publishers

394 Trichinosis: Muscle Histochemistry MUSCLE 8, NERVE SepIOct 1979

generalized muscle pain was present with both ac- tive contraction and passive stretching. There was no arthritis. Examination of mental status dem- onstrated a deficit only in the rate of performance of' cognitive function. The patient was unable t o open thc j aw or t o ext.riide the tongue completely. There was diffuse hypotonia and a 415 weakness in all muscle groups secondary to pain. Sensation was unimpaired. Tendon reHexes were uniformly depressed, and plantar responses werc flexor. Ini- tial and subsequent laboratory data are indicated in table 1.

The chest x-ray was negative; t.he ECG was nor- mal except for a sinus tachycardia; and thyroid, renal, and liver function tests were within normal limits. Tests for urine inyoglobin, stool ova and parasites, and blood cultures were all negative. Acute and convalescent titers for TrrchineEla (by ihe bentonite flocculation method) were both 1 :40 (diagnostic levels: 1 :5).

On May 24, 1977, electromyography revealed protuse fibrillation potentials in all muscles sam- pled in upper and lower limbs, as well as a m y - opathic pattern on voluntary contraction; inflam- matory myopathy was suspected. A deltoid muscle biopsy performed that day confirmed the diagno- sis of' trichinosis by demonstrating an in flamma- tory muscle disease that included many eosinophils and featured encysted larval forms. Particularly noteworthy was the absence of significant per-iph- era1 eosinophilia until three to four weeks into the illness, at which time the CK indicated diminishing muscle damage.

Muscle Histology and Histochemistry. There were multiple foci of acute inflammation around intra- muscular arterioles and venules and also between rnusclc fibers. An inflaniniatory f0cus was often found surrounding necrotic muscle fibers, which were sometimes invaded by mononuclear cells (fig.

1 A). The cells contributing the exudate were mostly mononuclear cells of various types, including his- tiocytes, plasma cells, and lymphocytes. Within blood vessels, eosinophil polymorpl.ionuclear cells were commonplace (fig. IB). Abnormal muscle fi- bers of increased volume and enhanced staining properties (heniatoxylin & eosin, modified Gomori trichrome) were a striking feature of the specimen; they often contained nematode larvae of 35-pm diameter. A clear halo separated the parasites from the sarcoplasm, which usually had a heterogeneous, patchy appearance (fig. IC and fig. 2.4 and €5). Pe- culiar ovoid inclusions (figs. 1B and 2B) that were probably histiocytes, with a homogeneous cytoplasm and a lighter rounded nucleus, were present close to the parasite in most infected fibers. All parasites reacted enzymatically to NADH-TR as well as to ATPase (fig. 2A), which suggested that they were alive. From the proportion of fibers which contained parasite in cross section, keeping in mind the approximate length of the parasites and the length of the fibers in the deltoid muscle, it appeared that most muscle fibers contained one or more parasites. Fibrosis was not a feature in this biopsy, and calcified encysted larvae indicating previous infections were not seen.

Clinical Evolution. The patient went home on May 25, 1977, but ret.urned four days later with mod- erate mental confusion and incapacitating muscle wcakness and pain. She had also developed partial flexion contractures of the elbows and ankles.

Because of suspected ericephalopathy and myo- carditis, the patient was treated with prednisone (40 mg/day) in divided doses. Initial improvement was followed by rapid deterioration; a similar chain of events occurred when the prednisone dosage was increased to 60 mg/day. Corticosteroids were continued for approximately one month without apparent benefit. During the first week of hospi-

Table 1. Clinicopathologic data derived during the illness

Measure

Date WBC POLY" STAB EOS" ESRd CK

May 19, 1977 5.1 72 12 0 57 1355 May 27, 1977 10.1 57 17 5 91 107 June 10, 1977 8.5 73 5 8 101 13 June 23, 1977 8.6 82 0 4 116 24 July 1 1 , 1977 9.3 79 4 2 96 e -

'POLY = polymorphonuclear neutrophils bSTA5 = stabnuclear neutrophh 'EOS = eosinophils

'No data awlable ESR = erythrocyte sedimentation rate

Trichinosis Muscle Histochemistry MUSCLE 8, NERVE Sep/Oct 1979 395

396 Trichinosis: Muscle Histochemistry

Figure 1 . (A) lnflamrnatory exudate in relation to blood vessel (v = venule) and between muscle fibers. Necrotic fiber undergoing phagocytosis appears near the center. Hernatoxylin and eosin (H&E), bar = 50 pm. (a) Two eosinophils within an intramuscular blood vessel. Note mild perivascular mononuclear exudate and a distended necrotic muscle fiber; two cells of unknown identity appear within (arrowheads). H&E, bar = 50 pm. (C) Tangential section through nematode larva within a necrotic muscle fiber. H&E, bar = 50 m.

MUSCLE & NERVE Sep/Oct 1579

talization, pulmonary function (vital capacity, peak flow, and forced expiratory volume in one second) rapidly deteriorated from 100% to 40%, at which point they stabilized. For six weeks, the patient re- mained immobile with excruciating pain on mo\e- ment. Contractures developed, notably affecting jaw opening. Two months after the onset of her illness, she was scarcely able to feed herself. Tran- sient congestive heart failure with pleural effusion ~7a5 treated with diuretics. The retinal hemor- rhages resolved, but the low-grade fever, tachycar- dia, and depressed mental status persisted.

Trichinosis Muscle Histochemistry

Figure 2. Serial cross sections stained or reacted for enzyme activity. Note the vigorous reactivity of nematode larva within distended necrotic muscle fiber. (A) Myosin ATPase (pH 4.60). (B) Modified Gomori trichrome. Note examples of invading cells (arrowhead), also indicated in figure 10. Double larval profile probably represents U-turn in single parasite. Common bar = 50 pm.

The patient was discharged after a three-month hospitalization markedly limited in activities of daily living. A year later, the patient was playing tennis again.

COMMENT

Trichinosis is caused by the neniatode Trichinella spimlis. Most cases in the United States today are acquired through the ingestion of undercooked pork or bear meat. Proper cooking or freezing of such meat, as well as commercial cooking of gar- bage led to pigs, has greatly reduced the incidence

MUSCLE & NERVE Sep/Oct 1979 397

of this disease.3 The infested meat consumed by this patient was probably locally produced and sold. Most cases are limited to several weeks of myalgias following a prodrome of diarrhea and abdominal cramping. Encephalitis and myocarditis are often observed transiently from infiltration by the larvae and from the resultant inflammatory response.l.' The larvae f-ail to encyst, however, out- side the skeletal muscle. Corticosteroids are indi- cated for such complications, as well as for symp- tomatic relief of severe myalgia. Thiobendazole is probably useful only in the earliest stages of infes- tation while the parasite is still in the gastrointes- tinal tract. Since the diagnosis in our patient was estabIished only after serial CK levels indicated that infestation had ceased, we elected not to treat her with this potentially toxic drug.

Ocular manifestations of trichinosis are usually limited to periorbital edema and conjunctival or scleral hemorrhages. Only scattered case reports of retinal hemorrhages can be found in the liter- ature, and most of these are from the turn of the ~ e n t u r y . ' , ~ The etiology of the retinal hemorrhages remains unclear, but they may well represent an

antigen-antibody reaction or may be secondary to a local reaction to the larval form.

Regarding the neuromuscular manifestations in our patient, the presence of profuse sponta- neous fibrillations in all muscles sampled is worthy of comment. Such evidence of muscle fiber dener- vation probably reflects disconnection of frag- ments of muscle fibers from their endplate regions due to focal muscle fiber necrosis, rather than pri- mary involvement of intramuscular nerve endings. We can offer no explanation for the unusually pro- longed and severe course of trichinosis in this patient.

REFERENCES

1 . David MJ, Cilo M, Plaitakis A, Yahr MD: Trichinosis: severe myopathic involvemcnt with recovery. Neurology (Minneap) 26:37-40, 1976.

2. Kramer MD, Aiia JF: Trichinosis with central netlious sys- tem involvement. N~uru logy (Minneap) 22:485-491, 1972.

3. Most H: Trichinosis-preventable yet still with us. N Engl J Med 298:1178- 1180, 1978.

4. Thompson WG: Trichinosis: a clinical study of fifty-two spo- radic cases. A m J Med Scz 140:157-166, 1910.

398 Trichinosis: Muscle Histochemistry MUSCLE & NERVE SepiOct 1979