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Emergency Medicine Atlas > Part 2. Specialty Areas > Chapter 20. HIV Conditions >

Primary HIV Infection

Associated Clinical Features

Clinical illness accompanies primary HIV infection in approximately two-thirds of patients, usually within several days to several weeks of exposure. Acute HIV infection is often undiagnosed or underdiagnosed in the ED setting. The most common symptoms after seroconversion include fever, malaise, headache, photophobia, sore throat, enlarged lymph nodes, arthralgias, abdominal pain, diarrhea, and a typically maculopapular rash with lesions on the face, neck, and trunk (Fig. 20.1). This rash is seen in over half of persons with symptomatic acute HIV infection and can have many presentations. The lesions are usually 5 to 10 mm in diameter and are erythematous, nonpruritic, and nontender. Mucocutaneous inflammation and ulceration of the buccal mucosa is also a common finding and distinctive feature. Less frequently, patients will demonstrate neurologic signs and symptoms consistent with meningoencephalitis, myelopathy, peripheral neuropathy, or Guillain-Barré syndrome. Therefore HIV infection should be considered in the differential diagnosis of aseptic meningitis. The acute illness usually lasts from a few days to two weeks. Laboratory studies may show lymphopenia and thrombocytopenia.

Figure 20.1

Primary HIV Infection A maculopapular rash is seen in over half of persons with symptomatic acute HIV infection. This less typical papular/vesicular rash was present in a patient with primary HIV infection. (Courtesy of Gregory K. Robbins, MD, MPH.)

Differential Diagnosis

Formerly considered to be similar to a mononucleosis-like viral syndrome, primary HIV infection does present with some unique features. Perhaps the most distinctive physical manifestation is the skin rash, which is rarely found in primary presentations of mononucleosis, toxoplasmosis, and cytomegalovirus infection. The rashes of rubella and roseola do not affect palms and soles. Other considerations in the differential diagnosis include hepatitis A or B, disseminated gonococcal infection, drug reactions, and secondary syphilis.

Emergency Department Treatment and Disposition

HIV testing is rarely performed in the ED owing to the difficulty of obtaining informed consent, lack of time for thorough counseling, and uncertain follow-up. Moreover, the diagnosis of acute HIV infection is difficult to make with standard serologic tests. Emergency physicians should take a careful history for HIV risk factors and should be cautious but honest in entertaining this diagnosis. Patients should be educated about safe sex and referred for further outpatient testing and evaluation. Prompt follow-up is critical, since immediate antiviral therapy is indicated for persons with acute HIV infection.

Clinical Pearls

1. Although historically HIV infection has been seen predominately in patients who belong to high-risk groups, the epidemiology is changing. When any sexually active patient presents to the ED with an acute, severe febrile illness, acute HIV infection should be included in the differential diagnosis.

2. Consider acute HIV infection as a potential etiology in patients with aseptic meningitis, pharyngitis, or a maculopapular rash.

3. Ensure proper follow-up for patients in whom the diagnosis of acute HIV infection is entertained.

Candidiasis Associated with HIV

Associated Clinical Features

Oral infections are seen in over half of all HIV patients. Oral candidiasis can occur at all stages of HIV disease. The severity of the infection depends on the degree of immunosuppression. The most common species is Candida albicans. Candida tropicalis can cause severe infections. Another 150 different species of Candida have become increasingly resistant because of the chronic use of systemic antifungal therapy.

Oral thrush is classified as pseudomembranous, angular, or erythematous. Pseudomembranous candidiasis involves removable whitish plaques on the tongue and buccal mucosa (Fig. 20.2). Patients with angular cheilitis demonstrate erythema and fissures at the angles of the mouth. Erythematous thrush appears as smooth red patches along the soft and hard palate. Oral candidiasis can be diagnosed clinically and by microscopic observation of hyphae with 10% KOH preparation.

Figure 20.2

Oral Candidiasis Removable whitish plaques on the palate are seen in this HIV patient with pseudomembranous candidiasis. (Courtesy of Thea James, MD.)

Esophageal candidiasis frequently accompanies oral candidiasis. The most common symptoms are dysphagia and odynophagia. Barium swallow and endoscopy aid in making the diagnosis. Typical findings observed with an air-contrast barium swallow are ulcerative plaques, causing filling defects along the long axis of the esophagus and producing the classic "shaggy" mucosal appearance. Endoscopy provides for the definitive diagnosis (Fig. 20.3), and allows the examiner to obtain biopsies and viral, bacterial, and fungal cultures.

Figure 20.3

Esophageal Candidiasis Endoscopy demonstrating esophageal candidiasis in this HIV patient. (Courtesy of Edward C. Oldfield III, MD.)

Like other conditions in immunocompromised patients, vaginal candidiasis can be severe, causing a whitish discharge and vulvar erythema. Women will commonly present to the ED for evaluation of vaginal candidiasis as their first clinical manifestation of the HIV infection.

Differential Diagnosis

HIV-related candidal infections must be differentiated from a variety of other entities, depending on the site of infection:

Oral	Esophageal	Vaginal
Cytomegalovirus	Cytomegalovirus	Chlamydial
Herpes simplex	Herpes simplex	Gonococcal
Hairy tongue	HIV esophagitis	Bacterial
HIV stomatitis	Medication-related ("pill esophagitis")
Kaposi's sarcoma	Mycobacterium avium intracellulare

Emergency Department Treatment and Disposition

Poor oral intake secondary to pain associated with severe oral or esophageal candidiasis can cause dehydration and malnutrition, sometimes requiring intravenous hydration and admission. Empiric treatment is appropriate in patients suspected of having esophageal candidiasis. Endoscopy should be performed in those patients whose symptoms do not improve in 3 to 5 days. There is no "standard" treatment for candidiasis in the HIV patient. Both oral and vaginal candidiasis can be treated with standard nystatin or clotrimazole troches. Alternatively, systemic treatment with either ketoconazole or fluconazole is usually effective for oral, vaginal, and esophageal candidiasis. For severe or refractory cases of candidiasis, amphotericin B is the drug of choice.

Clinical Pearls

1. Popular one-dose oral treatments for oral or vaginal candidiasis are associated with a high rate of relapse in HIV patients.

2. Consider possible drug interactions when prescribing antifungal medications. For example, the absorption of ketoconazole is impaired by the simultaneous administration of antacids and cimetidine. Ketoconazole levels are also decreased in patients taking rifampin or isoniazid. Because of these drug interactions, many clinicians favor the use of fluconazole, since lack of gastric acid or the presence of food does not affect its absorption. Fluconazole does raise the serum levels of warfarin, rifabutin, or sulfonylureas.

3. Ensure follow-up in 3 to 5 days when treating empirically for presumptive esophageal candidiasis.

4. Oral candidiasis is a poor prognostic sign, predictive of progression to AIDS in the HIV-positive patient.

Oral Hairy Leukoplakia

Associated Clinical Features

Caused by the Epstein-Barr virus, oral hairy leukoplakia is frequently encountered in HIV patients who present to the ED with unrelated symptoms. The patient may demonstrate characteristic filiform projections and whitish plaques along the side of the tongue (Fig. 20.4). The buccal mucosa may also be affected. Most often oral hairy leukoplakia is asymptomatic, although occasionally this condition can cause pain. The diagnosis is usually made clinically. However, definitive diagnosis can be made by biopsy, which characteristically reveals acanthosis and parakeratosis.

Figure 20.4

Oral Hairy Leukoplakia Filiform projections and whitish plaques along the side of the tongue are characteristic. (Courtesy of Briana Hill, MD.)

Differential Diagnosis

Commonly seen in HIV patients are numerous conditions that can be confused with hairy leukoplakia. These include oral candidiasis, geographic tongue, oral herpes simplex virus, cytomegalovirus, Kaposi's sarcoma, and idiopathic aphthous ulcerations.

Emergency Department Treatment and Disposition

Patients known to be HIV-positive can be educated and reassured. If the patient is symptomatic, zidovudine, oral acyclovir, or topical tretinoin may be prescribed in consultation with an infectious disease specialist.

Clinical Pearls

1. The presence of hairy tongue in a patient who is not known to have HIV requires follow-up and serologic testing and may expand the emergency physician's workup.

2. Hairy leukoplakia is rarely associated with conditions other than HIV.

3. Oral candidiasis can be distinguished by utilizing a swab in an attempt to remove the exudate characteristic of thrush and by observing pseudohyphal elements microscopically.

Kaposi's Sarcoma

Associated Clinical Features

Prior to the emergence of HIV, Kaposi's sarcoma (KS) was known only as a rare endothelial tumor found in older patients of European/Mediterranean descent. In HIV patients, KS most often affects male homosexual or bisexual patients. The etiologic agent, human herpesvirus 8, is strongly implicated as the viral cofactor that plays an important role in the development of KS.

Kaposi's sarcoma is usually multicentric, involving the skin and visceral organs. In lighter-skinned individuals, cutaneous KS is usually violaceous (Fig. 20.5), whereas it is black in those who are darker-skinned (Fig. 20.6). Visual presentations vary. Early lesions are usually less than 0.5 cm in diameter, nontender, and flat. Later they become larger and nodular. Any area of the skin can become involved, especially the soles of the feet and the mucous membranes. The palms are rarely affected.

Figure 20.5

Kaposi's Sarcoma A single violaceous patch is seen on the face of an HIV-positive patient. (Courtesy of George Turiansky, MD.)

Figure 20.6

Kaposi's Sarcoma Black KS lesions, as typically seen in darker-skinned individuals. (Courtesy of the Department of Dermatology, National Naval Medical Center, Bethesda, MD.)

Differential Diagnosis

Other conditions that can present similarly to Kaposi's sarcoma include drug reactions, melanomas, opportunistic infections, bacillary angiomatosis, and thrombotic thrombocytopenic purpura.

Emergency Department Treatment and Disposition

Since the diagnosis of cutaneous KS requires biopsy, the patient should be referred to dermatology and infectious disease for follow-up. Early KS can be treated with immunomodulators and antiviral agents, whereas late KS or rapidly progressive KS is treated with systemic chemotherapy or radiation therapy.

Clinical Pearls

1. HIV patients who present with persistent raised purple lesions warrant biopsy.

2. Perform a careful skin and oral examination in HIV patients.

3. Note that half of patients with oral involvement have other GI tract involvement as well.

4. KS can be an early manifestation of HIV infection in patients with normal CD4 cell counts.

Toxoplasma Gondii Infection

Associated Clinical Features

Toxoplasmosis is a common opportunistic infection affecting HIV patients with less than 100 CD4 cells/L. It can present as encephalitis, chorioretinitis, pneumonia, or a disseminated disease. The most common cause is reactivation of a latent infection.

Central nervous system (CNS) toxoplasmosis most often presents with symptoms consistent with a mass lesion (headache, focal neurologic deficit, seizure), or as encephalitis (fever and altered mental status). Diagnosis can be difficult. Contrast computed tomography (CT) of the head most typically reveals multiple ring-enhancing lesions with a predilection for the basal ganglia or corticomedullary junction (Fig. 20.7). Magnetic resonance imaging (MRI) of the head is a better test for the diagnosis. Serum serologic tests have no role in the diagnosis; however, cerebrospinal fluid (CSF) antibodies to T. gondii can be helpful. Often the diagnosis is based on response to empiric treatment, as evidenced by an improvement in symptoms and reduction in the size of the lesions.

Figure 20.7

Toxoplasma gondii Infection Contrast head CT showing typical multiple ring-enhancing lesions seen in T. gondii CNS infection. (Courtesy of Edward C. Oldfield III, MD.)

Ocular toxoplasmosis is a common complication of HIV disease. Patients typically present with a visual disturbance such as decreased vision, floaters, or visual field deficits. Eye pain or swelling is rare. Retinitis is typically diagnosed by indirect ophthalmoscopic evaluation revealing exudates and hemorrhage (Fig. 20.8). Toxoplasmosis retinitis appears different than cytomegalovirus (CMV) retinitis because it involves deeper strata of the retina, resulting in less edema and hemorrhage.

Figure 20.8

Toxoplasmosis Retinitis Ocular toxoplasmosis is a common complication of HIV disease. The lesion is a focal destructive chorioretinitis which leaves well-defined, heavily pigmented scars, especially in the macular area. (Courtesy of Department of Ophthalmology; Naval Medical Center, San Diego, CA.)

Differential Diagnosis

Other pathologic CNS conditions to consider may be classified as either infectious (bacterial meningitis, tuberculous meningitis, herpes encephalitis, progressive multifocal leukoencephalopathy, syphilis, fungal infections, etc.) or noninfectious (lymphoma, metastasis, drug reaction).

Ocular toxoplasmosis can appear similar to cytomegalovirus, varicella zoster, herpes simplex virus, Pneumocystis infection, fungal infection, ischemic retinopathy, ocular syphilis, and drug reactions.

Emergency Department Treatment and Disposition

Stabilization of the patient is the initial intervention for CNS toxoplasmosis. Subsequently, analgesics and antipyretics should be administered if indicated. If the patient presented with a seizure, the emergency physician should consider loading with intravenous phenytoin or fosphenytoin. The workup should include a noncontrast head CT followed by a contrast head CT and a lumbar puncture. Infectious disease consultation should then be obtained. When the diagnosis of CNS toxoplasmosis is made, treatment includes pyrimethamine and sulfadoxine for 6 weeks or until symptoms or neuroimaging findings have resolved. As in the case of Cryptococcus infections in HIV patients, chronic suppressive treatment is required. The dose of trimethoprim-sulfamethoxazole used for prophylaxis against Pneumocystis carinii pneumonia is sufficient.

For ocular toxoplasmosis, a thorough slit-lamp examination, including fluorescein staining and measurements of intraocular pressure, should be done before consulting ophthalmology.

Clinical Pearls

1. Space-occupying lesions, which are common in HIV patients, can cause increased intracranial pressure. Under most circumstances, perform a head CT before attempting a lumbar puncture in order to prevent iatrogenic herniation.

2. Consider steroids and seizure prophylaxis for patients with severe cerebral edema as evidenced by severe confusion, lethargy, coma, or even papilledema.

3. Educate patients with HIV to cook their meat thoroughly and to be compulsive about hand washing. Cat owners should be instructed to wear gloves while cleaning the litter box.

Cytomegalovirus Infections

Associated Clinical Features

Cytomegalovirus (CMV) infects over three-quarters of HIV patients, usually resulting from reactivation of a latent infection. Most patients have progressive disease with a CD4 cell count of less than 100/L. CMV infection can present as chorioretinitis, central nervous system disease, GI disease, or pulmonary disease.

Patients with ocular CMV typically complain of unilateral vision loss. If untreated, the condition progresses to bilateral blindness. The funduscopic examination usually reveals exudates, hemorrhages, edema, and dense opaque lesions, giving it the typical "cottage cheese and ketchup" appearance (Fig. 20.9).

Figure 20.9

Cytomegalovirus Retinitis Funduscopic examination shows exudates and hemorrhages ("cottage cheese and ketchup" appearance) seen with CMV retinitis. (Courtesy of Edward C. Oldfield III, MD.)

Differential Diagnosis

Although many opportunistic infections (fungal, toxoplasmal, herpetic) can mimic cytomegalovirus infections, the differential diagnosis should include ischemic retinopathy and drug reactions.

Emergency Department Treatment and Disposition

First-line therapy consists of either ganciclovir or foscarnet given intravenously. Intraocular ganciclovir implants can be combined with either. Relapse or progression of CMV retinitis is common, thus requiring chronic suppressive maintenance therapy.

Clinical Pearls

1. Because the diagnosis can be difficult, ocular complaints in HIV patients require a complete ophthalmologic examination and possible ophthalmology referral.

2. Unlike patients with candidal esophagitis, whose chief complaint is dysphagia, patients with CMV esophagitis typically complain of odynophagia or substernal chest pain and very infrequently of dysphagia.

3. Bone marrow suppression is a major toxic effect of ganciclovir.

Cryptococcal Infections

Associated Clinical Features

HIV patients infected with Cryptococcus neoformans can present with the disseminated form (Fig. 20.10) or with primary central nervous system (CNS) or pulmonary manifestations. Cryptococcal meningitis is a common opportunistic infection of the CNS, usually occurring in patients with advanced HIV infection whose CD4 cell counts are less than 50/L. Presenting symptoms are often nonspecific. Most commonly, patients with cryptococcal meningitis complain of headache, fever, and malaise that may be anywhere from 1 day to 4 months in duration. Diagnosis is made by lumbar puncture. Cerebrospinal fluid (CSF) findings usually reveal a normal CSF glucose concentration, a mildly elevated CSF protein concentration, and a CSF leukocyte count of less than 20/L. Although the sensitivity is not extremely high, an india ink stain in the ED can be beneficial (see Fig. 21.22). A CSF cryptococcal latex antigen test can also be obtained and has a sensitivity of 90%, as compared with 50% for an india ink stain. Definitive diagnosis is by culture.

Figure 20.10

Cryptococcal Infection Cryptococcal skin lesions in disseminated form. Note that the umbilicated centers give a similar appearance to that of molluscum contagiosum. (Courtesy of Briana Hill, MD.)

Differential Diagnosis

Diseases that might mimic cryptococcal meningitis include other fungal infections (Histoplasma and Nocardia), bacterial infections (bacterial meningitis, tuberculous meningitis, brain abscess), viral encephalitis (herpes simplex virus, herpes zoster, progressive multifocal leukoencephalopathy), protozoal infections (toxoplasmosis), and space-occupying lesions (lymphomas, Kaposi's sarcoma).

Emergency Department Treatment and Disposition

As with all patients, the most critical first step in the ED is stabilization. In general, HIV patients with fever and headache should receive an antipyretic and have blood for two cultures drawn. Empiric antibiotics (ceftriaxone, 2g IV) should be administered if the patient appears "sick" or has unstable vital signs. Empiric administration of antivirals or antifungals should be discussed with an infectious disease specialist. Most often the workup should include noncontrast computed tomography (CT) followed by contrast CT of the head and lumbar puncture (LP). If the lumbar puncture reveals cryptococcus, the standard treatment consists of amphotericin B with flucytosine for a period of 6 weeks. High cerebrospinal fluid (CSF) pressure can cause many of the symptoms of cryptococcal meningitis. Serial spinal taps, an indwelling lumbar drain, or ventriculoperitoneal shunting may be indicated. Fluconazole is the maintenance treatment of choice for cryptococcal meningitis.

Clinical Pearls

1. Perform the LP after the CT, and do so with the patient in a lateral position so as to obtain a proper opening pressure.

2. Obtain a fourth tube of CSF for special studies such as directogens (Haemophilus influenzaetype B, C. neoformans, Neisseria meningitides, Streptococcus pneumonia, Streptococcus agalactiae), acid-fast stains and cultures, VDRL, cytology, PCR (varicella zoster, enteroviruses, herpes simplex virus, parvovirus B19, JC 19 virus).

3. "False-positive" india ink stains can occur with other encapsulated organisms such as Klebsiella pneumoniae, Rhodotorula, Candida, and Proteus.

4. Blood cultures are positive in more than three-quarters of patients with cryptococcal meningitis.

Herpes Zoster in HIV Patients

Associated Clinical Features

In primary varicella infection, the virus migrates from the skin to the sensory nerves, where it becomes latent. This primary phase can be much more severe in HIV patients, sometimes causing central nervous system involvement, pneumonitis, and hepatitis. Contrary to patterns seen in immune-competent patients, primary varicella in HIV patients is more extensive, with deep-seated, slow-healing, and often recurrent lesions that may last for months.

Reactivation of the varicella virus (rarely HSV) characterizes herpes zoster, with acute inflammation of one or more of the dorsal root ganglia. A prodrome of lancinating pain and hyperalgesias over the skin surface for 3 to 4 days is followed by the appearance of a herpetic eruption of painful vesicles with red bases in a dermatomal distribution (Fig. 20.11). Reactivation herpes zoster is seen in 10 to 20% of HIV patients and is often the first clinical indication of an immune deficiency. Approximately 5% of patients will develop "zoster paresis," with a motor weakness following the rash.

Figure 20.11

Dermatomal Distribution of HZV Many tiny vesicles on an erythematous base are grouped in a dermatomal distribution in this HIV patient. (Courtesy of Jeffery Gibson, MD.)

HIV patients with herpes zoster are at risk for dissemination of the virus (Fig. 20.12), possibly leading to meningoencephalitis, retinitis, and pneumonitis. Cerebral angiitis is a complication of herpes zoster involving the ipsilateral carotid or middle cerebral artery, with subsequent contralateral aphasia or focal deficits. Reactivation of the virus in the ophthalmic division of the trigeminal nerve (Fig. 20.13) can cause conjunctivitis, keratitis, ocular muscle palsies, ptosis, and mydriasis.

Figure 20.12

Disseminated Herpes Zoster Infection Vesicles are seen over the entire face, representing disseminated HZV infection (multiple dermatomal distributions). (Courtesy of the Department of Dermatology, National Naval Medical Center, Bethesda, MD.)

Figure 20.13

Ophthalmic Herpes Zoster This patient has vesicles in the ophthalmic division of cranial nerve V bilaterally. (Courtesy of Daniel Savitt, MD.)

The diagnosis of herpes zoster in the ED is usually made clinically. Culture, serologic testing, or PCR confirms unequivocally. A Tzanck smear can be obtained by scraping the base of a lesion in an attempt to demonstrate multinucleated giant cells (see Fig. 13.15).

Differential Diagnosis

Etiologies for other vesicular lesions commonly encountered in HIV patients include herpes simplex virus, enterovirus, insect bites, contact dermatitis, and opportunistic infections.

Emergency Department Treatment and Disposition

Patients with disseminated disease or ophthalmic zoster should receive intravenous acyclovir (10 to 12.5 mg/kg IV q 8 h). Moreover, treatment of zoster ophthalmicus should include topical antibiotics and an immediate ophthalmology referral. For uncomplicated mild cases of herpes zoster, acyclovir (800 mg five times a day for 10 days) or famciclovir (500 mg tid for 7 days) is recommended. [Valacyclovir should be used with caution in HIV patients, since it is associated with thrombotic thrombocytopenic purpura (TTP).] Acyclovir or famciclovir cause a more rapid resolution of cutaneous lesions if started within 72 h of their appearance, but they do not change the incidence of postherpetic neuralgia. Valacyclovir may be more effective than acyclovir or famciclovir. In the absence of response to one of the oral regimens, the patient should be switched to intravenous acyclovir or foscarnet (if resistance is suspected). Immunocompromised patients should not be placed on steroids. Narcotics, capsaicin cream, and tricyclic antidepressants can be used for pain control.

From a preventive standpoint, the Centers for Disease Control (CDC) recommends that immunocompromised patients receive postexposure prophylaxis with varicella zoster immune globulin if they present within 96 h of exposure. Furthermore, susceptible patients should be vaccinated.

Clinical Pearls

1. Avoid prescribing oral antivirals and discharging patients home without close follow-up.

2. Worsening cases of herpes zoster, complicated herpes zoster, or ophthalmic zoster all require intravenous acyclovir and admission.

3. Herpes zoster encephalitis can occur months after the cutaneous phase and can be difficult to diagnose. Common presenting symptoms include mental status changes, headache, fever, photophobia, and vomiting. Ensure follow-up for patients diagnosed with shingles who are less than 50 years old, since they may require workup of a potential underlying immunodeficiency.

Eosinophilic Folliculitis

Associated Clinical Features

Eosinophilic folliculitis is a common dermatologic condition that usually involves the face, neck, trunk, and extremities (Figs. 20.14, 20.15). Patients complain of severe pruritus. The skin lesions usually start as small groups of pustules and vesicles. These can later coalesce to create irregular lakes of erosions and polycyclic plaques with central hyperpigmentation. Most patients with this condition will demonstrate CD4 cell counts of less than 250/L. Approximately half of these patients will have moderate eosinophilia and moderate leukocytosis.

Figure 20.14

Eosinophilic Folliculitis The rash of eosinophilic folliculitis consists of small groups of pustules and vesicles, as seen on the face of this patient. (Courtesy of the Department of Dermatology, National Naval Medical Center, Bethesda, MD.)

Figure 20.15

Eosinophilic Folliculitis A magnified view showing pustules at the base of each hair follicle. (Courtesy of the Department of Dermatology, National Naval Medical Center, Bethesda, MD.)

Differential Diagnosis

HIV patients have a high incidence of seborrheic dermatitis, which can be confused with this condition. Inquiry about concurrent medications or environmental exposures may suggest either a drug reaction or insect bites. Kaposi's sarcoma and lymphomas can present similarly to this condition. Other dermatologic conditions to be considered are scabies, staphylococcal folliculitis, photodermatitis, pruritus nodularis, xerostomia, and ichthyosis.

Emergency Department Treatment and Disposition

The diagnosis requires dermatology referral for biopsy. Antihistamines, topical steroids, itraconazole, and ultraviolet B phototherapy are effective.

Clinical Pearls

1. The severe pruritus associated with this condition helps distinguish it from bacterial folliculitis.

2. Patients with eosinophilic folliculitis may present with prurigo nodularis and lichen simplex chronicus as a consequence of severe itching and rubbing.

Herpes Simplex Virus in HIV Patients

Associated Clinical Features

As HIV infection progresses and the CD4 cell count declines, HSV infections become more frequent and severe, with delayed healing and prolonged shedding. The lesions can be oral, labial, esophageal, genital, or rectal (Fig. 20.16). These ulcerations are often associated with regional adenopathy. HSV esophagitis is often associated with oral or labial HSV. In contrast to cytomegalovirus (CMV) where there is a large solitary esophageal ulcer, multiple small ulcers characterize HSV esophagitis. Perirectal lesions are often beefy red and extremely tender, with a predilection for the gluteal cleft. Perirectal HSV may also be associated with proctitis and anal fissures.

Figure 20.16

Herpes Simplex Virus in an HIV Patient Severe, recurrent perirectal HSV lesions in an HIV patient. (Courtesy of Briana Hill, MD.)

Ocular HSV may be demonstrated by observing dendritic lesions after fluorescein staining (see Figs. 2-30, 2-31, and 2-32). HSV is associated with a syndrome of acute retinal necrosis characterized by pain, keratitis, and iritis that may lead to retinal detachment. Recurrent herpetic whitlow in HIV patients can be severe, with extensive cutaneous erosions on the fingers. Dissemination can cause encephalitis, pneumonitis, hepatitis, and colitis. The diagnosis is usually made clinically but can be confirmed a Tzanck preparation, biopsy, or culture.

Differential Diagnosis

Vesicular lesions such as those caused by contact dermatitis, herpes zoster, eosinophilic folliculitis, molluscum contagiosum, and drug reactions can resemble herpes simplex virus.

Emergency Department Treatment and Disposition

Acyclovir (200 mg five times a day for 10 days) or famciclovir (500 mg tid for 7 days) are standard treatments. Valacyclovir should be used with caution in patients with HIV since it is associated with TTP. Ocular HSV requires prompt ophthalmology referral. Severe, refractory, or disseminated HSV is an indication for admission and intravenous acyclovir. Intravenous acyclovir should be used with caution in dehydrated patients because it can crystallize in the renal tubules. For frequent recurrent oral or genital outbreaks, suppressive regimens (acyclovir 600 to 800 mg qd) are indicated.

Clinical Pearls

1. Anticipate disseminated disease in HIV patients.

2. Presentations of HSV may be atypical compared to HSV in immunocompetent individuals.

3. Suspect HSV in any HIV patient with a poorly healing, painful perirectal lesion.

4. Resistance to acyclovir and cross-resistance to ganciclovir are relatively common. Foscarnet may be considered as an alternative.

Molluscum Contagiosum

Associated Clinical Features

Molluscum contagiosum, usually an asymptomatic, benign disease, may be severe in HIV patients. The disease is caused by a poxvirus. HIV patients have a predilection for facial rash, sometimes with ocular involvement (Fig. 20.17). The rash can also involve the groin or become generalized. Typical presentations consist of groups of 2 to 20 small, discrete, "waxy" lesions with central umbilication. The incubation period for the virus ranges from 2 weeks to 6 months. Diagnosis is usually clinical but can also be made with a "squash" preparation—i.e., a Wright stain demonstrating intracytoplasmic inclusions.

Figure 20.17

Molluscum Contagiosum Facial rash with ocular involvement is a common site of infection in HIV patients. Note the central umbilication. (Courtesy of the Department of Dermatology, National Naval Medical Center, Bethesda, MD.)

Differential Diagnosis

Other dermatologic lesions that are often mistaken for molluscum contagiosum are cutaneous Cryptococcus, basal cell cancer, keratoacanthoma, and condyloma accuminata.

Emergency Department Treatment and Disposition

If the diagnosis is suspected in the ED, the patient should be reassured and referred to a dermatologist. The latter may utilize one of the following treatments: trichloroacetic peels, mechanical removal, cryosurgery, or the drug cidofovir. The recurrence rate is high.

Clinical Pearls

1. Although these lesions can regress spontaneously, removal is advisable to prevent autoinoculation.

2. Clinically, it may be difficult to distinguish between cutaneous Cryptococcus and molluscum contagiosum. Dermatology or infectious disease consultation and biopsy may be required.

Pneumocystis

Associated Clinical Features

Suspect Pneumocystis carinii pneumonia (PCP) in any HIV patient who presents with complaints of dyspnea and nonproductive cough. Presentations can be indolent, acute, or subacute. Associated symptoms include fever, fatigue, anorexia, weight loss, and chest pain. The CBC is usually normal except for lymphopenia. The LDH is often elevated. Arterial blood gases most often reveal a respiratory alkalosis and an increased A-a gradient. Findings on chest radiographs can be variable; however, the most common manifestation is diffuse interstitial alveolar infiltrates (Fig. 20.18). Previous recommendations that HIV patients with CD4 counts less than 200/L should receive lifelong prophylaxis are changing. Therefore emergency physicians may encounter this condition more frequently in the future. Definitive diagnosis requires observing organisms in lung tissue. The most sensitive method is by open-lung or transbronchial biopsy. However, the more common diagnostic method is bronchoscopy and bronchoalveolar lavage revealing organisms on methenamine-silver stain.

Figure 20.18

Pneumocystis carinii Pneumonia (PCP) Chest radiograph showing diffuse interstitial alveolar infiltrates of PCP. (Courtesy of Edward C. Oldfield III, MD.)

Differential Diagnosis

The differential diagnosis of an HIV patient presenting to the ED with a pulmonary complaint is broad. In terms of frequency, community-acquired bacterial pneumonias are at the top of the list. Inquiry about previous purified protein derivative (PPD) status, travel, and ill contacts are important. This history might lead the examiner to suspect tuberculous pneumonia, histoplasmosis, cryptococcosis, coccidioidomycosis, or aspergillosis.

Another important question is the CD4 nadir, which might lead to suspicion of cytomegalovirus or toxoplasmal infection. Sometimes the findings on the chest radiograph can help in making the diagnosis.

Emergency Department Treatment and Disposition

The first priority in treating PCP is general supportive care. Trimethoprim-sulfamethoxazole, orally or intravenously, is the standard treatment. Pentamidine, atovaquone, and clindamycin are also effective. A 5-day course of prednisone should be added if the P_O2 is less than 70 or the A-a gradient is greater than 35. This has been shown to reduce the rates of intubation and death. Formerly, HIV patients received prophylaxis for the following indications: CD4 cell count less than 200/L, unexplained fever for more than 2 weeks, or an episode of oral candidiasis. However, if the viral load and CD4 counts are under good control, many infectious disease specialists are now stopping PCP prophylaxis.

Clinical Pearls

1. Include PCP in the differential diagnosis of any HIV patient who presents with a persistent fever or respiratory complaint.

2. PCP can also affect the bone marrow, spleen, liver, GI tract, pancreas, palate, pericardium, thymus, central nervous system, or eyes.

Scabies

Associated Clinical Features

Human scabies is one of the most common contagious dermatoses; it is caused by the mite Sarcoptes scabiei. In HIV patients, this organism can cause "crusted scabies," also known as Norwegian scabies (see Fig. 13.62), which denotes an overwhelming scabies infestation. In typical scabies, the mites cause extremely pruritic burrows, vesicles, and papules (Fig. 20.19) in a characteristic distribution involving the finger webs, sides of the hands and feet, breasts, waist, and groin. In contrast, crusted scabies typically affects the hands and the feet with asymptomatic crusting. Norwegian scabies typically does not cause significant pruritus. Typical scabies involves approximately 15 mites per infected individual, whereas Norwegian scabies involves a hyperinfestation with thousands to millions of mites per individual. Scabies is spread by direct physical contact, and it can occur in epidemic form. Risk factors include poor hygiene, crowding, and exposure to pets.

Figure 20.19

Scabies Typical scabies rash showing unroofed papules secondary to scratching. Several small burrows are also seen. (Courtesy of George Turiansky, MD.)

Differential Diagnosis

Often, Norwegian scabies will not be included in the differential due to lack of pruritus. Other conditions to consider are drug reactions, which are extremely common in HIV patients, and pediculosis in sexually promiscuous patients and prostitutes. Dermatoses such as psoriasis and Kaposi's sarcoma should also be included in the differential diagnosis.

Emergency Department Treatment and Disposition

Most often the diagnosis of scabies is made clinically, with evidence of burrows and severe pruritus in a characteristic distribution. Definitive diagnosis is made from examination of shavings from the lesions. Placing mineral oil over a suspected lesion and then shaving it with a number 15 blade can demonstrate the mites, which are usually 0.3 to 0.4 mm in length. Sometimes eggs, egg casings, or feces can be seen. Norwegian scabies is diagnosed similarly, with demonstration of the mites on a mineral oil or potassium hydroxide microscopic examination.

Permethrin cream has a low toxicity and is the treatment of choice for scabies. Patients are instructed to apply the cream from the neck down and leave it on for 8 h before removal. The patient's clothes and bedding should be washed in hot water. Antihistamines alleviate the pruritus.

For HIV patients with Norwegian scabies, permethrin should be applied to the face, scalp, behind the ears, and from the neck downward. Repeat treatments may be needed. Sometimes 6%salicylic acid, a keratolytic agent, should be prescribed to improve penetration of the scabicide. For severe or refractory cases, oral ivermectin (200 g/kg for one dose) can be tried.

Clinical Pearls

1. Wear gloves!

2. Oral antibiotics are often indicated for Norwegian scabies because of skin breakdown.

3. Treat close contacts.

4. Tell patients that although the scabicide will kill the mites, the itching may last for weeks. Patients often seek repeat treatments and inappropriately receive additional scabicides, which can cause contact dermatitis.

Thrombocytopenia

Associated Clinical Features

Thrombocytopenia occurs in 30 to 60% of all HIV patients. It can occur independently at all stages of HIV infection and by itself does not have significant prognostic value. This is different from HIV-associated anemia and granulocytopenia, which occur concomitantly with the severity of the course of the HIV infection. The etiology of HIV-associated thrombocytopenia is usually multifactorial, with decreased bone marrow production and increased platelet destruction, which can be either immune- or nonimmune-mediated. Immune destruction occurs secondary to molecular mimicry between the HIV 120 antigen and the platelet GpIIb/IIIa receptor. Infections and fevers can decrease the life span of platelets in HIV patients, contributing to the thrombocytopenia. HIV patients with thrombocytopenia can present to the ED with bleeding (especially from the oral mucosa), ecchymosis (Fig. 20.20), and petechiae.

Figure 20.20

Thrombocytopenia Ecchymosis in an HIV patient with thrombocytopenia. (Courtesy of Edward C. Oldfield III, MD.)

Differential Diagnosis

The skin findings of thrombocytopenia can be confused with manifestations of opportunistic infections or Kaposi's sarcoma. If laboratory findings indicate a thrombocytopenia, the clinician should exclude pseudothrombocytopenia by assuring that the smear does not contain clumped megakaryocytes. Aside from primary thrombocytopenia associated with HIV, the emergency physician should consider drug toxicity, idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and infections.

Emergency Department Treatment and Disposition

The emergency physician's efforts are initially focused on stabilization of the patient with two large intravenous lines, type and cross-match, and crystalloid infusion if significant bleeding has occurred. Because of the complexity of the differential diagnosis and potentially complicated treatment of HIV thrombocytopenia, an infectious disease specialist should be consulted early. In most cases, HIV patients with platelet count greater than 50,000 can be managed conservatively. Zidovudine can increase platelet counts in over 50% of patients. If the platelet count is less than 20,000 many infectious disease specialists recommend gamma globulin infusion and parenteral steroids. Other possible treatments include dapsone, vincristine, and, as a last resort, splenecotomy. Even if the patient is to be managed conservatively, bone marrow analysis should be arranged on an outpatient basis to rule out other causes of thrombocytopenia.

Clinical Pearls

1. Observe universal precautions!

2. Perform thorough skin and oral examinations in all patients with HIV looking for evidence of thrombocytopenia.

3. Take a careful drug history and consider other infectious etiologies before assuming the thrombocytopenia is directly secondary to HIV infection.

4. Spontaneous bleeding is rare unless the platelet count is less than 10,000.

Drug Reactions

Associated Clinical Features

For unknown reasons, HIV patients have a 5 to 20 times higher rate of drug reactions than non-HIV patients. Up to 5% of ED visits by HIV patients are due to complications of pharmacologic therapy. Many of these reactions are manifest dermatologically, in order of decreasing frequency: (1) exanthems (Fig. 20.21), (2) urticaria/angioedema, (3) fixed drug reactions (see Fig. 13.46), (4) erythema multiforme (see Fig. 13.1), and (5) photosensitivity reactions (see Fig. 13.58). The most common classes of medications associated with rashes are antivirals, antibiotics, and antifungals.

Figure 20.21

Drug Reaction Exanthematous drug reaction in an HIV patient. (Courtesy of Kenneth Skahan, MD.)

Differential Diagnosis

In addition to cutaneous drug reactions, the emergency physician should consider other primary dermatologic conditions. Often the timing of drug initiation can be helpful. Most drug reactions occur within 1 to 2 weeks of the initiation of the drug, but they can also occur months or years later. Another consideration is that the skin findings may be a manifestation of opportunistic infection or neoplasm, such as Kaposi's sarcoma or lymphoma.

Emergency Department Treatment and Disposition

The emergency physician may need to consult an infectious disease specialist, a pharmacist, or a dermatologist to help clarify the existence of a drug reaction. Clues besides recent initiation of a new drug are eosinophilia greater than 1000 or elevated liver function tests. Individual treatment varies depending on the situation. The offending agent should be discontinued. Antihistamines and steroids are indicated in certain situations.

Clinical Pearls

1. Do not forget to ask about alternative medicines and nonprescription medications.

2. One-half of all HIV patients will react adversely to sulfa drugs.

3. Be aware of Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN).

4. Notify Medwatch or a similar hospital agency regarding serious or unusual reactions.

Acute Necrotizing Ulcerative Gingivitis

Associated Clinical Features

Acute necrotizing ulcerative gingivitis (ANUG), also known as Vincent's angina or trench mouth, is commonly seen in HIV patients (Fig. 20.22). The triad associated with ANUG is oral pain, halitosis, and ulcerations along the interdental papillae. Other signs and symptoms include "metallic taste," "wooden teeth" sensation, tooth mobility, fever, adenopathy, and malnutrition. The cause of this aggressive, destructive process is infection by oral anaerobes (Treponema, Selenomonas, Fusobacterium, Prevotella). ANUG represents a spectrum of disease from mild ulcerations to severe cellulitis and spread of the infection to the soft tissues, cheeks, lips, and bones.

Figure 20.22

Acute Necrotizing Ulcerative Gingivitis (ANUG) ANUG (Vincent's angina or "trench mouth") caused by spirochetal and fusiform bacteria in an HIV patient. Note the punched-out ulcerations of the interdental papillae, which are pathognomonic. (Courtesy of the Department of Dermatology, National Naval Medical Center, Bethesda, MD.)

Differential Diagnosis

The differential diagnosis includes typical gingivitis, pharyngitis, HIV-associated idiopathic ulcerations, herpes simplex virus, and oral candidiasis. Emergency physicians should always consider Ludwig's angina. Noma (cancrum oris, gangrenous stomatitis), a rare disease of childhood associated with malnutrition, is characterized by an anaerobic destructive infectious process of the orofacial tissues that can resemble ANUG.

Emergency Department Treatment and Disposition

ANUG is most frequently seen in three population groups: (1) HIV patients, (2) malnourished children, and (3) young adults who are under a great deal of stress. The first steps for the emergency physician are to eliminate other, potentially more serious life-threatening infections and to address hydration status. Treatment includes (1) eliminating contributing factors (stress, poor nutrition, poor sleep, alcohol and tobacco use), (2) chlorhexidine rinses twice a day, (3) surgical debridement by an oral surgeon, and (4) oral pencillin and metronidazole.

Clinical Pearls

1. Do not miss Ludwig's angina (brawny submandibular induration and tongue elevation—see Fig. 6.23) or noma.

2. ANUG is most frequently confused with herpes simplex virus.