Cutaneous larva migrans

A 21-year-old black man, a nonsmoker previously in good health, presented to the Letterman Army Medical Center Pulmonary Service after six weeks of nonproductive cough, headaches, fevers, anorexia, and a 4.5 kg (ten pound) weight loss. He denied dyspnea, hemoptysis, chest pain, high risk behavior for human immunodeficiency virus (HIV) infection, or gastrointestinal symptoms. He lived and worked in northern California with recent travel to Korea. He had received a ten-day course of erythromycin without relief of his symptoms.

Physical examination revealed a well-developed black man in no apparent distress, with a blood pressure of 124/72 mm Hg, a pulse of 80 beats per minute, a temperature of 40.5 [degrees] C, and respirations of 14 per minute. Chest examination was clear to percussion and auscultation. Cardiac examination revealed a grade 3/6 systolic ejection murmur at the lower left sternal border. There was no hepatosplenomegaly. Genitourinary examination was normal. Shotty, nontender lymphadenopathy was present in his left posterior cervical chain. Skin examination revealed a 1 x 2-cm soft, nontender, mildly erythematous nodular lesion at the right temporal region. The remainder of the examination was normal.

Laboratory examination showed a hematocrit value of 41 percent, platelet count of 833 x [10.sup.6]/L, and white blood cell count of 17.7 x [10.sup.9]/L with 48 percent segmented neutrophils, 3 percent band cells, 24 percent lymphocytes, and 25 percent eosinophils. Arterial blood gas on room air showed pH 7.43, [Pco.sub.2] of 5.0 kPa (38.1 mm Hg), and [Po.sub.2] of 11.9 kPa (89.7 mm Hg). Results from serum chemistries and urinalysis were normal.

Chest roentgenogram showed left perihilar lymphadenopathy and bilateral alveolar nodular infiltrates predominately in the lingula.

A diagnostic skin biopsy was performed. What is the likely diagnosis? (a) Sarcoidosis (b) Churg-Strauss syndrome (c) Loffler's syndrome (d) Coccidioidomycosis (e) Tropical filiarial eosinophilia

Answer: (d) Disseminated coccidioidomycosis

Biopsy of the temporal skin lesion demonstrated small, noncaseating granulomas with microabscesses, and an eosinophilic infiltrate without organisms. Cultures of the lesion subsequently grew Coccidioides immitis.

Patients with sarcoidosis may also have skin nodules, papules, and plaques, but eosinophilia is usually not seen. The chest roentgenogram can show a variety of abnormalities, but symmetrical bilateral hilar and paratracheal lymphadenopathy is classic. Churg-Strauss syndrome comprises the triad of eosinophilia, pulmonary infiltrates, and airflow obstruction. The skin manifestation is a palpable purpuric skin eruption caused by vasculitis. Loffler's syndrome, usually caused by parasites, drugs, and environmental agents, is characterized by peripheral eosinophilia and eosinophilic pulmonary infiltrates. It can be associated with skin lesions, as in cutaneous larva migrans. Tropical filarial eosinophilia, due to Wuchereria bancrofti and Brugia malayi, causes extreme eosinophilia. Lymphatic tracts may become inflamed, and abscesses can form, but not other skin lesions are usually seen.

Discussion

Coccidioidomycosis is a geographically limited infection with a wide spectrum of illness, ranging from mild, self-limited, and clinically unrecognized infection to widely disseminated and potentially life-threatening disease.

Coccidioides immitis is a dimorphic fungus, found in the soil as an arthrospore and in human tissue as a round-walled spherule. It is found in semi-arid climates with short, intense rainy seasons, such as central California, Arizona, West Texas, New Mexico (the Lower Sonoran life zone), Mexico, and Central and South America. Except for rare cases of direct skin innoculation, infection in humans is by inhalation of the highly infectious arthrospores. Infectivity is enhanced by dry and windy conditions or activity that stirs up the soil (construction, archaeologic digging, and agricultural work). While infection is most common in these endemic areas, cases have been reported thousands of miles away, presumably through contaminated fomites. The diagnosis should be considered even in nonendemic areas.[1]

Primary pulmonary infection is asymptomatic in at least 60 percent of cases; most often the illness is so mild that positive skin testing or chest roentgenogram changes are serrendipitous findings. The remaining 40 percent of cases have symptoms varying from mild flu-like illness to severe pneumonia. Eosinophilia is common, with counts usually from 3 to 26 percent of the total white blood cell count. Skin findings occur in 5 to 25 percent of patients. Erythema nodosum is characterized by tender, red nodules on the lower legs ("desert bumps"). Erythema multiforme is seen less frequently and occurs as a maculopapular rash on the extremities, often with vesicles or bullae. "Valley fever" comprises a constellation of cough, malaise, erythema nodosum, and arthralgias. This form of disease is thought to indicate a hypersensitivity reaction to the fungus; it usually lasts two to six weeks and has a good prognosis.[2] Most cases of primary pulmonary infection show complete resolution of the chest roentgenogram findings, though some infiltrates form coin lesions, or coccidioidomas. A small number of cases progress to a chronic form, with cavity formation, lung volume loss, and a slow relapsing course over many years.

Roentgenographically, primary pulmonary coccidioidomycosis most often shows nonspecific alveolar infiltrates. These can be distinguished from other pneumonias by three specific findings: (1) hilar lymphadenopathy, often bilateral, is seen in about 20 percent of cases; (2) "phantom infiltrates" that resolve in one lung segment and reappear in another; and (3) thin-or-thick-walled peripheral lung cavities that develop over a period of days.[3]

Disseminated coccidioidomycosis occurs rarely, but is a serious complication that may involve many organ systems, especially the skin, bones, joints, meninges, and genitourinary system. Dissemination appears to be more likely in male subjects, dark skinned races (Mexicans, Blacks, Filipinos, and Native Americans), children, the elderly, immunosuppressed patients, and, possibly, pregnant women.[2] Dissemination occurs early in the disease course, within a few months of pulmonary infection, and may be invoked by immunosuppressive agents (such as corticosteroids, chemotherapy, and HIV infection).

The skin is the most commonly affected organ system in disseminated disease.[4] Skin eruptions consist of verrucous granulomas, subcutaneous abscess, and indolent ulcers. Verricous lesions are commonly found on the face and nasolabial folds. Several lesions found together may suggest a more malignant course of disease. These lesions initially show epithelial thickenings and grow to resemble common warts. Occasionally, microabscesses form and caseating necrosis may occur. Spores are found in the tissue and in multinucleated giant cells. Abscesses are usually not tender, warm, or erythematous, and they are usually seen under the arm and on the back or hip. The abscesses usually have a necrotic center surrounded by a granulomatous infiltrate of lymphoid cells, plasma cells, epithelial cells, and giant cells. Fungal spores are abundant in these lesions. Chronic ulcers can form draining sinus tracts and are found over the joints of the foot, ankle, and hands.[2,5] There are reports of skin as the only organ system affected.[5] These cases are rare in occurrence and are thought to be due to direct innoculation of the skin in laboratory personnel.

Diagnosis is made by culture of sputum, skin lesions, visceral lesions, or urine, as well as with skin testing and serologic testing such as latex particle agglutination and complement fixation.[1]

Primary coccidioidomycosis is self-limited and no treatment is usually necessary. Antifungal therapy, usually with amphotericin B, is required with progressive or disseminated disease. The toxicities of amphotericin B (local phlebitis, anemia, renal impairment, cardiovascular effects, and neurological symptoms) have led to attempts to resolve Coccidioides infections with other agents, such as ketoconazole and itraconazole.[6]

The prognosis of primary pulmonary coccidioidomycosis is excellent, with usual total resolution of disease, or, at worst, residual evidence on chest roentgenogram. Progressive pulmonary disease and disseminated disease have much more varied outcomes, ranging from total resolution to recurrent pneumonia-like episodes to rapid death (us with untreated meningitis).

Our patient showed no evidence of other extrapulmonary infection. He was treated effectively with 2.0 g of intravenous amphotericin B with complete resolution of all evidence of infection.

This patient presented with pulmonary coccidioidomycosis and an isolated skin lesion which was the sole manifestation of disseminated infection. This is unusual but has been reported.[7] Close examination of the skin remains an invaluable tool in the initial assessment of the patient with pulmonary disease.

References

[1] Drutz DJ, Catanzaro A. Coccidioidomycosis: Part I. Am Rev Respir Dis 1978; 117:559-85 [2] Drutz DJ, Catanzaro A. Coccidioidomycosis: Part II. Am Rev Respir Dis 1978; 117:727-71 [3] Bayer AS, Fungal pneumonias: pulmonary coccidioidal syndromes (part I). Chest 1981; 79:575-83 [4] Lever W. Fungal diseases. In: Lever W, ed. Histopathology of the skin. Philadelphia: JB Lippincott, 1983; 328-55 [5] Carroll GF, Haley LD, Brown JM. Primary cutaneous coccidioidomycosis: a review of the literature and a report of a new case. Arch Dermatol 1977; 113:933-36 [6] Knoper SR, Galgiani JN. Systemic fungal infections: diagnosis and treatment. I. Coccidioidomycosis. Infect Dis Clin North Am 1988; 2:861-75 [7] Schwartz RA, Lamberts RJ. Isolated nodular cutaneous coccidioidomysis: the initial manifestation of disseminated disease. J Am Acad Dermatol 1981; 4:38-46

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