Post-transplant Infections 10.31

Viral Meningitis

FIGURE 10-60 VIRAL MENINGITIS Viruses causing meningitis in transplant recipients. The presentation is usually with fever and headache alone or in conjunction Causal agents Coronavirus with headache may be the initial symptom. Nuchal rigidity is rare in the transplant Enterovirus HIV patient. Cerebrospinal fluid samples should Coxsackie* Influenza A, B be saved for viral analysis and analysis ECHO* Lymphocytic choriomeningitis virus should be requested if the diagnosis is not Poliovirus Parainfluenza virus rapidly available from standard studies. Adenovirus Rabies virus Rhinoviruses Arbovirus Rotavirus Herpes group† Japanese encephalitis virus* Cytomegalovirus* Tick borne encephalitis virus virus 1 and 2* PML (JC) virus (in development)* HHV-6* BK virus (in development)* HHV-8* Varicella-zoster virus* Epstein-Barr virus*

* Cerebrospinal fluid polymerase chain reaction available to make the diagnosis but locations vary † Increased in transplant patients

Black Hairy

FIGURE 10-61 (see Color Plate) Black hairy tongue is the result of hypertrophy of filiform papillae of the tongue, often seen in transplant patients after antibiotic treatment. The origin is unknown but is associated with topical or systemic antibiotics, poor , , alcohol, and the use of mouthwashes. Most often there are no symptoms; however, nausea, gagging, taste alteration, or halitosis are reported by some patients. Treatment includes brushing with a soft brush and, occa- sionally, topical vitamin B, salicylic acid, gentian violet, or surgical removal. This entity is not to be confused with hairy , which is composed of white corrugated plaques on the lateral sur- face of the tongue. These lesions may be small and flat or exten- sive and hairy. Microscopic evaluation shows epithelial cells with herpetic viral inclusions, specifically Epstein-Barr virus. Treatment is oral acyclovir. 10.32 Transplantation as Treatment of End-Stage Renal Disease

Tinea Versicolor

FIGURE 10-62 (see Color Plate) Tinea versicolor (pityriasis versicolor) is a chronic superficial fungal disease caused by Malassezia furfur, a yeast normally found on the skin. It is in yeast form in the unaffected skin areas and in the mycelial phase on affected skin. The disease usually is located on the upper trunk, neck, or upper arms. Symptoms may include scal- ing, erythema, and pruritis. It may appear as slightly scaly brown macules or whitish macules. Treatment options include oral or topi- cal terbinafine (1% cream or gel), oral or topical ketoconazole, oral fluconazole, or topical treatments, such as ciclopiroxolamine, piroc- toneolamine, zinc pyrithione, or sulfur-containing substances, such as selenium sulfide; the most common treatment is selenium. Patients are asked to wet themselves in the shower, turn off the water, apply the selenium and let it sit for 10 minutes, and then rinse. Also, oral fluconazole, 200 mg, once or repeated once a week later is a simple and effective treatment. Of note, oral terbinafine, 250 mg, daily for 12 weeks is associated with slightly decreased cyclosporine levels. Terbinafine is an allylamine that binds to a small subfraction of hepatic cytochrome P450 in a type I fashion. Side effects seen during terbinafine use include gastrointestinal dis- tress in up to 5% of patients and skin rashes in 2% of patients.

Kaposi’s Sarcoma

FIGURE 10-63 (see Color Plate) Kaposi’s sarcoma of the lower leg in a male transplant recipient. Kaposi’s sarcoma is a tumor, perhaps of lymphatic endothelial origin, that presents as purple papules or plaques that advance to nodules of the extremities, , or viscera. In transplant recipients it pre- sents on average by 21 months post-transplant, with the largest num- ber (46%) within the first post-transplant year. It is seen most often in men (3:1) and in those of Arabic, black, Italian, Jewish, and Greek ancestry. It accounts for 5.7% of the malignancies reported to the Cincinnati Transplant Tumor Registry (nonmelanoma skin cancers and in situ carcinomas of the uterine cervix excluded). Transplant programs in Italy and Saudi Arabia have reported higher rates of post-transplant Kaposi’s sarcoma. Visceral involvement is less com- mon in the transplant recipient than in the AIDS patient, but it must be remembered that it may be seen in the liver, lungs, gastrointestinal tract, and nodes. Mortality is increased with visceral involvement (57% versus 23%). HHV-8 has been proposed as the causal agent of this tumor; however, not all investigators feel the evidence is con- clusive. Of note, the occurrence in AIDS patients is decreased in those who receive foscarnet, cidofovir, and ganciclovir, but not acyclovir. Treatment includes decreasing immunosuppression, local radiation, excision, interferon, or chemotherapy. Post-transplant Infections 10.33

Mucormycosis

Most of the spores, once in the tissue, are contained by the phago- cytic response. If this fails, as it often does in patients with diabetes mellitus and those otherwise immunosuppressed, germination begins and hyphae develop. The hyphae, as shown in the micro- graph, are large, nonseptate, rectangular, and branch at right angles. Infection begins with the invasion of blood vessels, which causes necrosis and dissemination of the infection. The most common site of involvement is the rhino-orbital-cerebral area, accounting for approximately 70% of cases; however, pulmonary, cutaneous, gas- trointestinal, and disseminated infection may be seen. The chest radiograph during pulmonary infections may show an infiltrate, nodule, cavitary lesion, or pleural effusion. Gastric involvement may range from colonization of peptic ulcers to infiltrative disease with vascular invasion causing perforation. Although classic for mucormycosis, a black eschar of the skin, nasal mucosa, or is present in only about 20% of patients early in the course of the dis- FIGURE 10-64 ease and cannot be relied on for assistance in early diagnosis. Mucormycosis is caused by fungi of the order Mucorales, including Survival is dependent on early diagnosis. Diagnosis is by Rhizopus, Absidia, and Mucor. Mucorales are ubiquitous sapro- with classic histologic findings and by culture of tissue. Treatment phytes found in the soil and on decaying organic material, including includes amphotericin B, surgical removal of the lesion, packing of bread and fruit. Human infection is believed to be caused by the the sinus areas with amphotericin B–soaked packs, and perhaps inhalation of spores that initially land on the oral and nasal hyperbaric oxygen. Liposomal amphotericin B has also been effec- mucosa. Direct inoculation into tissues, however, has been reported. tive. Treatment must include both surgery and amphotericin B.

Condyloma Acuminata

A B

FIGURE 10-65 Condyloma acuminata (anogenital/venereal ) are caused by interferon alpha. Lesions have responded in 50% of nontransplant infection with human papillomavirus 6 or 11. In transplant recipi- patients receiving the 5% cream. Invasive treatments have included ents they may become extremely extensive. Treatment has included surgical excision, cryotherapy, electrocautery, and carbon dioxide fluorouracil, podophyllin, podophyllotoxin, intralesional interfer- laser. Recurrences are common. A, Condyloma acuminata in a on, topical interferon, systemic interferon, and, more recently, male transplant recipient. B, Condyloma acuminata in a female imiquimod, which causes the induction of cytokines, especially transplant recipient.