International Journal of Dermatology, Vol. 34, No. 8, August 1995

CAMEO

HICKMAN CATHETER-^ASSOCIATED PRIMARY CUTANEOUSASPERGILLOSIS IN A PATIENT WITH THE ACQUIRED

IMMUNODEFICIENCY SYNDROME

LAURA S. ROMERO, M.D., AND STEVEN J. HUNT, M.D.

A 37-year-old white man with acquired immunodeficiencysyndrome (AIDS) presented with a 3-day history of fever, pain,and erythema around a left subclavian Hickman catheter thathad been placed 4 months earlier for hyperalimentation be-cause of intractable nausea, vomiting, and diarrhea fromgastrointestinal cryptosporidiosis. The patient had experi-enced two previous localized line-infections of this catheter(caused by Enterobacter and Staptiylococcus aureus), andhad recently completed a course of vancomycin for the lat-ter. His medical history included recurrent perirectal herpessimplex and oral hairy leukoplakia. The most recent CD4count, 4 months earlier, was 67 x 10̂ per liter. Medicationsincluded ondansetron, paromomycin sulfate, monthly aero-solized pentamidine, and fentanyl patches.

On admission, the patient exhibited erythema, warmth,and induration of the left chest around the Hickman cath-eter, without evidence of discharge. A verrucous plaquewas noted incidentally several centimeters below thecatheter. The catheter was removed, an associated tract ab-scess was incised, drained, and cultured, and the patientwas started on intravenous vancomycin and ceftazidime.Cefazolin was substituted for the latter, after the abscessculture grew Staphylococcus aureus sensitive to cefazolin.Blood cultures remained negative and a sputum culturegrew Candida. A chest film was clear and a white blood cellcount was 3.2 x 10̂ per liter with the following differential:.76 neutrophils, .07 bands, .12 lymphocytes, and .05 mono-cytes. Electrolytes and liver function tests were normal.

The dermatology service was consulted on the 2nd hospi-tal day to evaluate an erythematous plaque on the left chestwall. The plaque was asymptomatic and had been slowlygrowing for several months. Physical examination revealed a1.8 X 2.0 cm verrucous plaque with scattered micropustules(Fig. 1) located 4 cm inferior to the previous Hickman cath-eter site. There was no associated lymphadenopathy.

A punch biopsy revealed ulceration, acute and chronicdermal inflammation, and microabscess formation withseptate hyphae branching at 45 degree angles (Fig. 2). Fun-gal culture yielded organisms identified as aspergillus fumi-gatus. Special stains and cultures were negative for otherorganisms.

Therapy with intravenous amphotericin B was started ata dose of 0.6 mg/kg/day (30 mg) and the left chest plaque

From the Division of Dermatology, University of Galiforniaat San Diego Medical Genter, San Diego, Galifornia.

Address for correspondence: Laura S. Romero, M.D., UGSDMedical Genter, Division of Dermatology, 200 West ArborDrive, San Diego, GA 92103-8420.

was treated locally with daily cleansing, bacitracin oint-ment, and sterile gauze dressings. The patient was dis-charged after receiving 450 mg amphotericin, whereuponthe amphotericin dose was reduced to 30 mg per week. Theleft chest plaque decreased modestly in size but his generalhealth slowly deteriorated over the next 2 months. He wasadmitted to a hospice for comfort care and died one monthlater. No autopsy was performed.

DISCUSSION

Aspergillus is second only to Candida in causing fungalinfection in the immunocompromised host.' Cutaneousaspergillosis can occur as primary or secondary infec-tions. The latter are acquired either through hematoge-nous dissemination or from direct invasion of the skinfrom underlying structures (e.g., the paranasal sinuses ororbits).' Secondary cutaneous aspergillosis occurs in 5 to11% of patients with disseminated fungal infection.'"^Blood-borne emboli usually arise from tbe lungs, withthe initial infection being a necrotizing broncbopneumo-nia.-̂ Aspergillus fwnigatus is the most common speciesof Aspergillus involved in secondary cutaneous infectionand occurs most frequently in patients immunocompro-mised by malignancy or organ transplantation."*-^

Primary cutaneous aspergillosis is most often associ-ated with local skin injury (i.e., areas of local traumaaround intravenous catheter sites and macerated sitescaused by adhesive tape and arm boards).^-* Lesions

Figure 1. An erythematous plaque with micropustules ispresent (biopsy site located at inferior aspect).

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International journal of DermatologyVol. 34, No. 8, Augnst 1995

Figure 2. Septate hyphae of Aspergillus AIX- \ isible in themidst of mixed dermal inflammation, (hematoxylin and eosin,magnification x 400)

may present as hemorrhagic uleers with eschar forma-tion, molluscum contagiosum-like papules, necrotizingdermal plaques, or as erythematous indurations withoverlying pustules.'"^'^ Two cases of patients with atransplant developing asymptomatic subcutaneousnodules caused by cutaneous aspergillosis bave beenreported.^'^ Aspergillus flavus is the most commonlyimplicated Aspergillus species in primary cutaneous in-fections."*'̂ Of the approximately 40 cases of primarycutaneous aspergillosis in the literature to date, all buttwo have occurred in patients immunocompromised bycancer or posttransplant immune suppression.* Thosetwo cases occurred in patients with AIDS. This is there-fore the tbird case reported in a patient with AIDS.

Aspergillus infection is commonly associated withseveral host factors: underlying malignancy, especiallylymphoma/leukemia, prolonged neutropenia (>3 weeks);corticosteroid therapy; and broad spectrum antimicro-bial therapy. '̂'̂ '̂ -'-^^ Early initiation of antifungal ther-apy is associated with increased survival.' Neutropeniais a strong risk factor for aspergillosis because func-tional neutrophils are thought to be the primary hostdefense.'"'1^ In addition, the pbagocytic activity ofmacrophages is believed to be important. Suppressionof macrophage activity by corticosteroids places indi-viduals on such therapy at increased risk.'"-'^

Aspergillus infection is not generally considered tobe an opportunistic infection of AIDS. This is becausecell-mediated immunity is not tbe main defense againstAspergillus.^'^ The risk factors for aspergillosis in AIDSpatients are similar to those in other immunocompro-mised groups. One large study found 74% of AIDS pa-tients with invasive aspergillosis to have either receivedcorticosteroids or to have been neutropeoic (absoluteneutrophil count < 1.0 x 10' per liter or white bloodcell count < 2.0 x 10' per liter) before the itifection.Moreover, 75% of the patients had the lung as theirportal of entry, similar to that in the non-AiDS group.'°

Patients with AIDS atid aspergillosis are distinct inthat a significant percent (e.g., 26% in the above men-tioned study) have intravenous drug use as a potentialsource for their fungal contamination.'"''^ In severalinstances, HIV-positive intravenous drug abusers withAspergillus endocarditis or liver abscess secondary tohematogenous dissemination were thought to havecontracted the disease from contaminated needles.'''•^^In addition, AIDS patients witb aspergillosis have ahigher incidence of central nervous system dissemina-tion, 55% compared to 10-25% in non-AlDS immuno-compromised patients. Finally, patients with AIDS bavea very high mortality with aspergillus infection, ap-proaching 100% despite systemic antifungal therapy.'"

Treatment for invasive aspergillosis is associatedwith modest results. Hematogenous recovery fromneutropenia is often the crucial factor determining theresponse.*"''^'' Treatment modes have included highdose amphotericin B (1-1.5 mg/kg/day, to a total doseof 2 g),'^ sometimes with concomitant use of 5-fluoro-cytosine or rifampin for additive effects;' itraconazole(200-400 mg/day),''-' and, in cases of well localized in-fection, surgical excision.' Unfortunately, the poor CNSpenetration of itraconazole makes it less desirable fortreatment of AIDS patients, who are at increased riskfor central nervous system dissemination.'"

Treatment of primary cutaneous aspergillosis in-cludes systemic antifungal therapy, along with localwound care and removal of predisposing agents (e.g.,occlusive tape and infected catheters). Treatment withamphotericin B can result in resolution,^ but dissemi-nation and death tnay occur despite therapy, especiallyin patients who are persistently neutropenic.^ A com-bined approach using surgical removal and systemicantibiotic therapy such as amphotericin B or itracona-zole has also proved successful.^'^

DRUG NAMES

amphotericin B: Fungizonebacitracin ointment: Baciguentcefazolin sodium: Ancef, Kefzolceftazidime: Fortaz, Tazidimefentanyl: Duragesic Transdermal Patchesfentanyl citrate: Innovar, Sublimaze5-fluorocytosine: Ancobonitraconazole: Sporanoxondansetron bydrocbloride: Zofranparomomycin sulfate USP XXpentamidine aerosol: Nebupentrifampin: Rifadin, Rifomycin, Rimactanevancomycin dihydrate: Vancocin, Vancoled

Acknowledgment:patient.

David M. Amron, M.D., referred this

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Primary Cutaneous Aspergillosis in AltisRomero atid Hunt

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8. Greenbaum RS, Roth JS, Grossman ME. Subcutaneousnodule in a cardiac transplant. Arch Dermatol 1993;129:1189-1194.

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12. Gerson SL, Talbot GH, Hurwitz S, et al. Prolongedgranulocytopenia: the major risk factor for invasive pul-monary aspergillosis in patients with acute leukemia.Ann Intern Med 1984; 100:345-351.

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15. Brunetti FC, Carnevale E, Dughetti G, et al. Ultrasono-graphic and microbiological diagnosis of mycotic liverabscesses in patients with AIDS. Microbiologica 1989;12:101-104.

16. Denning DW, Tucker RM, Hanson LH, et al. Treat-ment of invasive aspergillosis with itraconazole. Am JMed 1989; 86:791-800.

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Coal Tar

During the 19th century, European and American cities were lit by gas lamps thatburned illuminating gas, principally carbon monoxide, a by-product of tbe con-version of coal to coke for tbe manufacture of steel. Another by-product, whichwas considered worthless, was coal tar. During the 1830s, Friedlieb F. Runge, a40-year-old chemist, bad been given funds for unspecified research and facilitiesin an old castle, which had been converted to a cbemical factory, in Oranienburg,approximately 20 kilometers north of Berlin. He wondered whether anythingcould be done with the huge vats of coal tar that were accumulating. The coal tarwas too messy to dump. Nobody wanted it; nobody knew what to do with it.Prussia had a toxic waste disposal problem.

Runge obtained fractions from coal tar that he characterized and named: car-bolic acid (be was the first to identify phenol), rosolic acid (still used by tbis namein the dye industry but better known as pararosolic acid or aurin), pyrrole (dearto porphyrin chemists and "hemoglobinologists"), leukol (a white oily substancelater renatned quinoline), brunolic acid (a brownish oily substance, perhaps an-thracene), and kyanol (frotn Greek, blue oil), a dark violet-blue oily distillate thatreversibly formed colorless crystals on acidification. In 1834, he reported that"coal tar seems to be pretty rich in kyatiol." Forty years later, when the structureof kyatiol was shown to be aminobenzene, it was renamed a«»7ine (;j;7, an Arabicadjective, means "the blue"; tbe Nile is also "the blue" river of Egypt). Duringthe course of his research, Runge devised the analytic technique of paper chro-matography, which is still widely used VIi centuries later. From Fairbanks VF.Blue gods, blue oil, and blue people. Mayo Clin Proc 1994; 69:889-892.

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