BRIEF CLINICAL OBSERVATIONS

patient with superficial thrombophlebitis during multiple venipunctures for analgesics and replacement therapy with frozen and lyophilized plasma [3]. Thrombosis of an arteriovenous fistula 4 days after graft puncture has been described in a hemophilia A patient who used the graft for parenteral analgesics and FVIII concentrate [4]. Arterial occlusion occurs rarely in patients with hemophilia A. Unstable angina and fatal myocardial infarction due to documented right coronary thrombosis during FVIII concentrate replacement therapy have been described in two cases [5,6]. In their review, Goodnough et al [3] reported seven cases of myocardial infarction, with one complicated by a stroke, unrelated to FVIII replacement therapy. Cerebral thrombosis was also reported in one patient following evacuation of a subdural hematoma under FVIII concentrate coverage [7]; in another patient, widespread cerebrovascular occlusion by eosinophilic particulate matter has also been reported after FVIII concentrate infusion [8]. Thrombosis is a well-described complication of prothrombin complex therapy, and is likely due to the presence of activated clotting factors [2,3]. FVIII concentrates do not contain activated clotting factors, but preparations other than the high purity concentrates may contain particulate matter [9]. This debris has been shown to reduce the singlebreath diffusion capacity of carbon monoxide [9] and may have contributed to cerebral thrombosis in one patient [8]. This material may also play a pathogenetic role in the development of pulmonary hypertension observed in some of these patients

Foothills Hospital Calgary, Alberta, Canada 1. Levine Hoffman principles 2. Kasper

PH, Brettler DB. Clinical aspects and therapy for hemophilia A. In: R. Benz EJ Jr, Shattil SJ, Furie S. Cohen HJ. editors. Hematology: basic and practice. New York Churchill Livingstone, 1991: 1290-1304. CK. Postoperative thromboses in hemophilia B. N Engl J Med 1973;

289: 160. 3. Goodnough LT, Saito H, Ratnoff OD. Thrombosis or myocardial infarction in congenital clotting factor abnormalities and chronic thrombocytopenias: a report of 21 patients and a review of 50 previously reported cases. Medicine (Baltimore) 1983: 62: 248-55. 4. Barasz M. Spontaneous thrombosis of an arteriovenous fistula in a hemophiliac Am Fam Physician 1978; 18: 23-6. 5. Kopitsky RD. Geltman EM Unstable angina associated with factor VIII concentrate therapy for hemophilia A. Ann Intern Med 1986; 105: 2156. 6. Small M. Jack AS, Lowe GDO, Mutch AF, Forbes CD, Prentice CR. Coronary artery disease in severe haemophilia. Br Heart J 1983; 49: 604-7. 7. lchinose A, Maruyama I, Yoshida Y, lgata A. Cerebral thrombosis in a haemophiliac. Thromb Haemost 1981; 45: 190. 8. Ghatak NR, Husain MH. Unusual intravascular material in the brain. Am J Clin Pathol 1976; 65: 508-12. 9.8oese EC, Tantum KR, Eyster ME. Pulmonary function abnormalities after infusion of antihemophiliac factor (AHF) concentrates. Am J Med 1979; 67: 474-6. 10. Goldsmith GH Jr, Baily RG, Brettler DB. et al. Primary pulmonary hypertension in patients with classic hemophilia. Ann Intern Med 1988, 108: 797-9. Submitted

June 5. 1992, and accepted

June 22, 1992

RESOLUTIONOF HIV RETINITISWITH ZIDOVUDINETHERAPY

Multiple opportunistic infections of the retina have been described in patients with human immunodeficiency virus (HIV) infection [l]. HIV itself can infect the retina, but a clear relationship with clinical disease has not yet been established [2-4]. We report the case of an asymptomatic HIV-infected WA. Our hemophilia A patient developed symptomatpatient who presented with retinitis that resolved ic deep venous thrombosis while he was receiving with zidovudine therapy. FVIII concentrate alone for an orthopedic surgical Case Report. A 34-year-old homosexual man procedure. Common coagulation disorders associ- presented to the Infectious Disease outpatient clinated with thromboembolic risk were not present ic with blurred vision in the right eye. On funduscoand he was otherwise healthy. Orthopedic proce- pit examination, frank retinitis was seen in the lowdures are commonly associated with thromboemer portion of the right retina, with multifocal fluffy bolic complications in normal individuals, and it is white patches and sheathing along the inferotempossible that hemophilia patients undergoing these poral vessels (Figure 1, arrow). Fluorescein angiogprocedures with FVIII replacement do develop raphy revealed patchy and perivascular hyperdeep venous thrombosis more frequently than hithfluorescence (Figure 2). This patient was a previerto believed, but perhaps these are asymptomatic, ously asymptomatic HIV-1-seropositive man. His and hence not detected. Management of thrombosis temperature and the results of physical examinain hemophilia patients following surgery can be dif- tion were normal. A latex agglutination test for ficult. Heparin therapy in our patient was associ- cryptococcal antigen in the serum, and serologic ated with bleeding and a compartment syndrome, tests for toxoplasmosis and syphilis were negative. despite the administration of FVIII concentrate de- Although cytomegalovirus (CMV) was not cultured signed to maintain FVIII levels above 0.5 U/mL, from the blood, a diagnosis of CMV retinitis was considered, and the patient was treated with intrawith a disastrous outcome. BRUCERITCHIE, MJ). venous ganciclovir (10 mg/kg/d) for 4 weeks. His RICHARD C. WOODMAN,MJ). MAN-CHIU POON,M.D. vision did not improve, however, and the results of a University of Calgary funduscopic examination performed at the end of 700

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Figure 1. Photograph of the right fundus of the patient on first admission, demonstrating perivascular white patches and sheathing along vascular arcades (arrow).

Figure

the ganciclovir treatment were unchanged. His CD4 cell count was 355/pL at that time. The HIV-l p24 antigen level in the serum was extremely high (6,950 pg/mL) and prompted us to measure HIV-l plasmatic viremia according to the method of Coombs et al [5,6]. A high titer of plasmatic viremia was detected (312 tissue culture infective dose [TCID] 5O/mL), and treatment with zidovudine (600 mg/d) was initiated because of suspected HIVrelated retinitis. A rapid resolution of plasmatic viremia as well as a rapid decline in HIV-l p24 antigenemia was observed with zidovudine therapy. The patient’s vision then improved, and funduscopit examination, performed 2 months after initiation of zidovudine therapy, showed complete resolution of the retinitis. Plasmatic viremia was negative at that time, with an 89% reduction of HIV-l p24 antigenemia, and 445 CD4 cells/pL. Results of funduscopic examination remained normal during the lo-month follow-up of this patient, who is still receiving zidovudine therapy, and did not demonstrate any opportunistic infection. Comments. A variety of retinal disorders have been reported in patients with HIV-l infection. CMV retinitis seems to be the most frequent opportunistic infection of the retina, but Toxoplasma, Candida, syphilis, herpes simplex, and varicella zoster may also cause retinitis [1,7]. Early CMV retinitis may be difficult to diagnose, and this diagnosis was considered in our patient. However, the

inability to recover CMV from the peripheral blood, along with the failure of ganciclovir therapy and a CD4 cell count above 35O/pL, all militate against that diagnosis. Also, our patient had no evidence for other opportunistic pathogens that could affect the retina. A high percentage of patients with AIDS-related complex or AIDS can also demonstrate cotton-wool spots in their retina [l]. However, the white perivascular infiltrates with sheathing along vascular arcades in our patient were typical of retinitis and different from the dense, white, peripapillary lesions typical of cotton-wool spots. Furthermore, the appearance on fluorescent angiography, with hyperfluorescence in areas of perivascular exudates, was not consistent with that diagnosis. Interestingly, our patient demonstrated a high HIV-l burden in his peripheral blood. The high HIV p24 antigenemia and HIV-l plasmatic viremia we found in peripheral blood are unusual in a patient with more than 350 CD4 cells/pL [5,6]. We thus considered that HIV-l itself may have caused retinitis in this case. HIV-l can indeed infect the retina, and positive staining for HIV-l antigens has been found in the cytoplasm of endothelial cells as well as in neuroretinal cells [2-4]. The localization of HIV-l to endothelial cells within the retina is consistent with the hypothesis that virus-induced vascular alterations may result in retinitis. It was not clear from previous reports how-

showing

2. Fluorescein patchy

perivascular

angiogram obtained hyperfluorescence

December 1992 The American Journal of Medicine

at the

same

time,

(arrows).

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BRlEF CLINICAL OBSERVATIONS

ever, whether HIV-l itself could lead to clinical retinitis [2-4]. We therefore initiated zidovudine therapy in our patient, and noted within 2 months a clearance of plasmatic viremia, a strong decline of p24 antigenemia, and a complete resolution of the retinitis. Since zidovudine can cross the bloodbrain barrier, the effect observed in the blood may well have been observed in the retina. We believe we therefore have strong evidence in this case for retinitis that was very likely caused by HIV-l, and cleared after the institution of zidovudine therapy. JEAN-MICHEL MOLINA, MB. FRANCOISE FERCHAL, hm.

Saint-Louis Hospital Paris, France PATRICIA MARCEL, MB.

Pitie-Salpetriere Hospital Paris, France FREDERIC MORINET, MB. JACQUES MODAI, M.D.

Saint-Louis Hospital Paris, France 1. Holland GN, Kre@er AE. Neuroophthalmology of acquired immunodeficiency syndrome. In: RosenMum ML, Levy RM. Bredesen DE. AIDS and the nervous system. New York: Raven Press, 1988: 103-20. 2. Pomerantz RJ, Kuritzkes DR, De La Monte SM. eta/.Infection of the retina by human immunodefickmcy virus type 1. N Engl J Med 1987; 317: 1543-7. 3. Cantrill HL. Henry K. Brooks J. Erice A, Ussery FM, Baifour HH Jr. Recovery of HIV from ocular tissues in patients with AIDS. Ophthalmology 1988; 95: 1458-54. 4. Skolnik PR, Pomerantz RI, de la Monte SM. eta/. Dual infection of retina with human immunodeficiency virus type 1 and cytomegalovirus. Am J Ophthalmol 1989; 107: 361-72. 5. Coombs RW. Co&r AC, Allain JP. eta/.Plasma viremia in human immunodeficiency virus infectfon. N Engl J Med 19as. 321: 1626-31. 6. RouziouxC, Puel J, Agut H. et al. Comparative assessment of quantitative HIV viremia assays. AIDS. In press. 7. Bloom JN, Palestine AG. The diagnosis of cytomeBalovirus retinitis. Ann Intern Med 1988; 109: 963-8. Submitted

April 28, 1992. and accepted

(ACKNOWLEDGMENT: This work has been supported Netionale de Recherche sur fe SIDA and the CERI.)

July 10, 1992

in part by the Agence

FAILURETO RESPONDTO DEXAMETHASONE WITH FATAL CONSEQUENCES,AFTER INITIAL RESPONSETO MULTIDRUGTREATMENT IN A CASE OF AMIODARONE-ASSOCIATED THYROTOXICOSIS Amiodarone-associated thyrotoxicosis (AAT) is a life-threatening complication because it develops in cardiac patients and because classical treatments may be (1) ineffective (thionamides), (2) inapplicable (radioiodine), or (3) risky (thyroidectomy). Recently, two controlled studies have demonstrated the successful use of perchlorate [l] and prednisone [2] in combination with a thionamide in AAT. Moreover, four patients were cured by perchlorate and methimazole, although they continued to take amiodarone [3,4]. In five patients, the response to 702

Becember 1992 The American Journal of Medicine

perchlorate was slow but present [3]. Prednisone but not subsequent perchlorate failed to achieve euthyroidism in two reported cases, and perchlorate failed in one of eight patients [l]. One patient needed thyroidectomy because of severe persistent hyperthyroxinemia and required massive doses of drugs (dexamethasone, perchlorate, iopanoic acid, methimazole) to control triiodothyronine (T8) production [5]. From these published reports, combined medical treatment seems effective in controlling AAT. There is only one reported case of sudden death after partial relapse of thyrotoxicosis despite continuation of initially successful prednisone [6]. We describe a patient in whom the thyroid hormone concentration failed to respond to high doses of dexamethasone, with fatal consequences. A 60-year-old man was admitted to the hospital because of hyperthyroidism and unstable angina in July 1991. He had an acute myocardial infarction in 1976. He received 200 mg amiodarone daily, 5 days a week since 1988 for a transient episode of atrial fibrillation associated with heart failure. Angina pectoris developed in June 1990 and remained stable with a multidrug regimen. In July 1991, the patient complained of loss of weight and worsening of angina. Hyperthyroidism was diagnosed (Figure 1). Thyroid antibodies were negative, results of thyroid ultrasonography were slightly heterogeneous, and thyroid volume was 15 mL (normal less than 20 mL). Amiodarone was discontinued and perchlorate and methimazole were prescribed (Figure 1). Sixteen days later, the symptoms were unchanged. Total T8 and T&hyroid-binding globulin (TBG) had increased (Figure 1). Addition of dexamethasone induced normalization of total T8 and T8/TBG. After the patient was discharged from the hospital, the free thyroxine index (FT41) was normal, the dexamethasone dosage was reduced, and perchlorate was withdrawn after 40 days. At the beginning of September, serum free Tq (FT& and free T8 (FT8) increased. An increase of the dose of dexamethasone resulted in a transient reduction in serum free hormone concentrations that was not sustained. The patient was rehospitalized because of worsening angina, severe amyotrophy, and weakness. Episodes of atrial tachycardia and refractory ventricular fibrillation occurred and the patient died. Eighteen hours before the patient died, serum thyroxine (T&“I’BG, T&‘BG, and T8/T4 ratio were higher than at the time of amiodarone withdrawal. The initial increase in serum T8/TBG concentrations together with the sustained elevation of serum T&?BG prompted us to add corticoids at high doses to the treatment with methimazole and perchlorate. The subsequent normalization of serum

Volume 93

Resolution of HIV retinitis with zidovudine therapy.

BRIEF CLINICAL OBSERVATIONS patient with superficial thrombophlebitis during multiple venipunctures for analgesics and replacement therapy with froze...
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