RESIDENTS’ CLINIC 33-Year-Old Woman With Marked Eosinophilia Bairta Lassmany, MD*; Constanmne Tstcxriis, MD#; AND Aumiasi Vink, MD 33-year-old previously healthy woman presented to her local primary care physician with a 2-week his tory of chest pain, myalgia, headache, and right arm weak ness. Initial evaluation (reference ranges shown paren- {hetically) revealed @ white blood cell count of 25 x 10"/L (35-105 x 10%L) with a differential of 71% eosinophils (0%-7%), 10% lymphocytes (16%-52%) and 19% newtro- phils (42%-75%). Serum cardiac biomarkers were el- evated, and 12-lead electrocardiography revealed T-wave inversions in leads HL IT, V,, and V,, She was admitted to her local hospital for further evaluation, where transtho- racic echocardiography showed a normal ejection fraction and no regional wall motion abnormalities. Coronary an- ‘tiography yielded normal findings. Magnetic resonance imaging of the head performed because of her right arm ‘weakness revealed multiple foci of cortical and white mat- ter signal abnormalities involving the frontal, parietal, and ‘occipital lobes. The patient was transferred to our institu- tion for further evaluation and management. On admission to our institution, the patient complained of intermittent bilateral visual changes described as “squig- sly lines” in her field of vision, tunnel vision, and bilateral flashing lights. She denied fever, chills, cough, shortness of | breath, palpitations, abdominal discomfort, nausea, vorit- ing, diarrhea, or weight fluctuations. She had recently com- pleted a course of amoxicillin, which had been prescribed for an upper respiratory tract infection. ‘The patient had lived in South Dakota her entire life and had no history of travel outside the United States. She had 11 cats, which had occasionally brought dead birds and snakes into her home, and 2 puppies. She denied consump- tion of raw meat or fish, However, she reported that during the previous summer, she and her sister, who had preg- rnaney-induced pica, had eaten dirt dug ftom a hole in her backyard. The patient had a long-standing history of aloo- hol abuse but denied intravenous drug use. She smoked 10 cigarettes daily and chewed tobacco. She had depression “Resident in ntemal Meine, Mayo Schoo of Graduate Medel Eaves, ‘Majo Gini Caege of wade, Restos, Minn. ‘alow in lfecioes Oseases, Nays sero! of Graduste Heel Eaveaten, Majo Cone Cotage of Hedaina, Rochester, rn. {yaaa esoatan felon ahd Contant noctous Disses, Moyo Cine Cotege of Nessie, Rochester, ‘See end fate for cnet snawers to guestons \nduidleprs of this rt re not aside. Aatress corespondence to bbinash Vire, MD, Ousin of neous Osaaees, Nayo Cine Caloge of ‘edn, 260 Few St SH, Rochester, WA S508, {©2007 ay Foundation for Meal Hécaton and Research and anxiety disorder, which were being treated with escitalopram and lorazepam. ‘Examination at our institution yielded the following re- salts: temperature, 37.3°C; blood pressure, 104/73 mm Hg: pulse rate, 5 beats'min; respiratory rate, 2/min; and oxy gen saturation, 100% while breathing room air. The patient had mild weakness of the digit extensor muscles of the right hand and the right hypothenar muscle. Right upper-extrem- ity deep tendon reflexes were increased compared to those on the left. Ophthalmologic examination revealed normal findings. Heart rhythm was egular and no heart murmurs or rus were noted. Results of abdominal examination were "unremarkable; no hepatosplenomegaly was evident. The re- ‘mainder of the physical examination findings were norm 1.On the basis of the patient's initial history and presen- tation, which one ofthe following disorders is the most likely explanation for the eosinophilia? Infection 1. Medication :. Malignancy Atopy Hypereosinophitie syndrome Acquired eosinophilia (eosinophil count >0.5 x 10%/L) can be classified as either primary or secondary. With the exception of hypereosinophilic syndrome, all the choices listed are examples of secondary eosinophilia. Our pa- tient’s social history and abrupt onset of symptoms make an infectious cause of her eosinophilia most likely. Medi- cation-induced eosinophilia from her previous course of paRD Se ‘and self-limited. Our patient had marked eosinophil which is rarely seen in malignant diseases. Atopy is an inherited predisposition that can be associated with mild ‘eosinophilia. Typically, atopy causes eczema (atopic der- imatitis, allergic rhinitis, and allergic asthma, conditions that our patient did not have. The hypereosinophilic syn- romes are disorders marked by sustained overproduction of eosinophils. Diagnosis requires (1) sustained eosino- philia (absolute eosinophil count 21.5 x 10") for at least 6 months; (2) target-organ damage such as involvement of the heart lungs, skin, or nervous system; and (3) exclusion of other etiologies of eosinophilia. Our patient did not meet these diagnostic criteria because she had recent onset of symptoms and newly diagnosed eosinophilia, Initial evaluation at our institution included normal chest x- ray results. The erythrocyte sedimentation rate was 8 mivh Mayo Clin Proc. * January 2007:82(1):103-106 + www mavoclinicproceedingszom 103RESIDENTS CLINIC Enzyme immunoassays were negative for human immuno- ‘deficiency virus types 1 and 2. Given the patient's exposure to puppies, her consumption of soil, and the marked eosino- philia, an underlying parasitic infection was suspected asthe most likely cause of the patient's eosinophilia, 2, Which one of the following parasitic diseases is the ‘most likely cause of this patient's eosinophilia? 4. Giardiasis b. Cysticercosis €. Trichinosis 4, Strongyloidiasis €. Toxocariasis Disease-causing parasites can be classified into 2 main sroups: protozoa, which are unicellular organisms, and hel- ‘minths, which are complex multicellular worms. Protozoan infections such as giardiasis normally do not cause eosino- Dhilia, Helminths, which include nematodes (roundworms), ‘cestodes (tapeworms), and trematodes (flukes), are typi- cally associated with eosinophilia, Marked eosinophilia is usually seen when helminths invade and migrate through tissues. Eosinophitia commonly occurs early in cysticercosis, when the Taenia solium larvae spread hematogenousty and listibute within the brain and other tissues. Our patient did ‘not have the cerebral lesions typical of cysticercosis on MRI examination, Trichinosis usually causes high-grade eosino- philia. Common in Southeast Asia, it is associated with ingestion of undercooked pork or other meats such as bear, horse, or walrus. Initial symptoms include nausea, vomiting, diarthea, and fatigue, followed by fever, arthralgia, and my- gi, which is associated with elevated creatine kinase lev- ls. Our patient didnot consume raw or undercooked meats and did not travel outside the United States. Bary, often high-grade, eosinophilia is commonly seen in Strongyloides infections. Strongyloidiasis is endemic in tropical and sub- tropical regions of the world and occurs sporadically in temperate areas, The highest rates of infection inthe United ‘States occur in residents of Appalachia and the southeastem states, Our patient had not traveled to these areas, The infec- tion can be asymptomatic, may. cause intermittent urticaria, ‘or may lead to gastrointestinal symptoms sch as pain, bloat- ing, or diaries, symptoms our patient did not have. ‘Toxocariasis is common worldwide and can cause ‘marked eosinophilia’ It is usually caused by infection ‘with the dog roundworm (Taxocara canis), or less com- ‘monly, the cat roundworm (Toxocara cati). T canis exes ‘are excreted by puppies and are found in soil. Toxocariasis| typically affects young children who eat ditt. Our patient had 2 puppies, and she had consumed ditt the previous summer. We highly suspected Toxocara infection in our patient. 04 Mayo Clin Proc 3. Which one of the following tess is the best choice 10 confirm the patient's suspected underlying condition? 4a. Tissue biopsy and histologic diagnosis 'b. Enzyme-linked immunosorbent assay (ELISA) 4. Polymerase chain reaction €. Stool examination €. Urine examination Tissue biopsy and histology would reveal a definitive iagnosis* but are not indicated at this time because of the availability of less invasive tests. When toxocariasis is suspected clinically, the serum Toxocara ELISA should routinely be used to detect antibodies and to confirm the diagnosis. Currently, no polymerase chain reaction proce- dure is available for diagnosing toxocariasis. Stool exami- nations are unrewarding for toxocariasis caused by T canis oor T caté because these helminths do not mature to adult ‘worms in the intestinal tract of humans, and therefore, n0 eggs are shed in stool. Tcanis and T cati are not shed in the urine, Cysticercosis IgG antibody evaluation by Western blot was negative, and ELISA was negative for Trichi- nella antibody. However, results of Toxocara ELISA were positive, 4. Which one of the following isthe best treatment option for this patient? 4a. No treatment is needed b. Albendazole ©. Corticosteroids 1. Albendazole and corticosteroids . Pratiquantel ‘Treatment is required in symptomatic patients," and albendazole isthe treatment of choice. It should be given as a Sday course of 400 mg twice daily. For patients with severe symptoms of systemic toxocariasis or visceral larva rigrans (VLM), corticosteroids in conjunction with ant- hhelmintic therapy are recommended. Corticosteroids alone are not indicated for the treatment of VEM. In contrast, for patients with ocular involvement only oF with ocular larva rigrans (OLM), corticosteroids and surgery are the main- stay of therapy. Anthelmintic therapy may not completely eradicate the helminths from the eyes. Combined cortico- steroid and anthelmintic therapy has been helpful in sup- pressing the associated intense inflammatory reaction and is recommended in patients with severe respiratory, myo- ‘cardial, or central nervous system (CNS) involvement. Praziquantel is used to treat various helminthic infections, but itis not recommended for toxocariass, Our patient was treated with a 5-day course of alben- dazole and received high-dose prednisone that was slowly tapered + January 2007:82(1):103-108 + wwe mayoctnicproceedingscomRESIDENTS CLINIC FIGURE 4. Lite eyele of Toxocara canis. From the Centers for Disease Control and Prevention (awe d.ode.g0v/apc 5. To prevent reinfection, which one of the following options would be most helpful? 4. No reinfection is possible because the patient is now Prophylactic anthelmintic therapy - Counsel the patient on how to avoid infection |. Advise the patient not 1a have dogs . Vaccination Reinfection with T canis or T eatéis possible, and prior in- fection does not provide immunity. Prophylactic anthelmin- tic treatment has no role in preventing reinfection. Efforts to prevent infection must be directed at increasing awareness, especially that of pet owners, about potential zoonotic haz- ards and how to minimize them. Counseling this patient about the dangers of pica, a well-documented risk factor for toxo- catiasis, is essential. Advising the patient to not have dogs ‘would be extreme and unnecessary. No vaccine is currently available to provide protection from toxocara infection. ‘Ata L-month follow-up vist, the patient's eosinophilia, hhad resolved. Her overall condition had improved clini- cally, although she continued to have residual right upper- extremity weakness. The patient was counseled about pre- venting fusther infection with Toxocara, specifically, avoiding the consumption of dit DISCUSSION ‘Toxocariasis is a common parasitic disease that is caused primarily by T canis, a roundworm of dogs and other canid hosts? T cati, a roundworm found in cats and other fetid hosts, is a less common cause of toxocariasis. Toxocariasis can lead to a wide spectrum of diseases, including asymp- tomatic infection, isolated eosinophilia, VLM, and OLM. Knowledge about the life cycle of T canis is essential to ‘understanding the pathogenesis and clinicat manifestations of toxocariasis (Figure 1). Dogs and other canids are the efinitive hosts of T canis. The adult T canis worms live inthe intestines of dogs, most commonly in puppies, and proxluce eges that are excreted into the environment. Adult {female T canis worms can produce 200,000 eggs per day. and dogs infected with multiple adult worms could poten- tially excrete millions of eggs into the environment each ay. T canis eggs are excreted in the soil and usually Mayo Clin Proc. + January 2007:82(1:103-108 + www mayoclinicroceeings com 105