Case 20-2017: A 48-Year-Old Man With Weight Loss, Confusion, Skin Lesions, and Pancytopenia

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Case Records of the Massachusetts General Hospital
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Eric S. Rosenberg, M.D., Nancy Lee Harris, M.D., Editors
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Emily K. McDonald, Sally H. Ebeling, Production Editors
Case 20-2017: A 48-Year-Old Man

with Weight Loss, Confusion, Skin Lesions,
and Pancytopenia
Shibani S. Mukerji, M.D., Ph.D., R. Gilberto Gonzalez, M.D., Ph.D.,
Rajesh T. Gandhi, M.D., and Stefan Kraft, M.D.
Pr e sen tat ion of C a se

From the Departments of Neurology Dr. Robert H. Goldstein (Medicine): A 48-year-old man was seen in the emergency
(S.S.M.), Radiology (R.G.G.), Medicine department of this hospital because of confusion.
(R.T.G.), and Pathology (S.K.), Massachu‑
setts General Hospital, and the Depart‑ The week before this presentation, the patient, who was a lawyer, had traveled
ments of Neurology (S.S.M.), Radiology alone to Mexico for vacation. His family reported that he seemed to be in his
(R.G.G.), Medicine (R.T.G.), and Pathology usual health before the trip but that, when they spoke with him by telephone while
(S.K.), Harvard Medical School — both
in Boston. he was in Mexico (4 days before this presentation), he seemed euphoric and easily
distracted, which were notable changes from baseline. They were then unable to
N Engl J Med 2017;376:2580-9.
DOI: 10.1056/NEJMcpc1616401 reach him by telephone for 72 hours and became increasingly concerned about his
Copyright © 2017 Massachusetts Medical Society. well-being. Ultimately, he was reached by telephone; he was agitated and refused
to board his scheduled return flight. The patient’s mother traveled from the
United States to Mexico, where she found the patient to be confused and unkempt
and to have lost his wallet and passport; he was drinking alcohol and insisting
that he needed to travel immediately to New York City to work on an important
legal case. His mother escorted him on a flight back to the United States and
brought him to the emergency department of this hospital for evaluation.
In the emergency department, family members reported that the patient had
begun having unexplained weight loss approximately 1 year earlier. The patient
reported a history of multiple nonmelanoma skin cancers that had been treated
with cryotherapy; he had also adopted a diet low in added sugar, which he believed
had led to improvement in the appearance of the skin lesions. He had undergone
sigmoidoscopy 12 years earlier to remove a foreign body from the sigmoid colon.
He took melatonin and was allergic to penicillin. He was single, lived alone in an
urban area of New England, and frequently traveled to Mexico; he had sex with
men and used condoms intermittently. He drank alcohol in moderation and did
not smoke or use illicit drugs. There was no family history of dementia, stroke,
seizure disorder, cancer, depression, bipolar disorder, or schizophrenia.
2580 n engl j med 376;26 nejm.org June 29, 2017
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Case Records of the Massachuset ts Gener al Hospital
On examination, the patient appeared thin A

and agitated. The temperature was 35.8°C, the
pulse 71 beats per minute, the blood pressure
120/62 mm Hg, the respiratory rate 16 breaths
per minute, and the oxygen saturation 99%
while he was breathing ambient air. He was alert
and oriented to which city he was in and to the
year but not the month. When he was asked why
he was in the emergency department, his re-
sponse revealed anosognosia and confabulation.
He had nonfluent aphasia and perseverated when
speaking, but he had no dysarthria and was able B
to repeat words, name objects and the current
president, and pantomime brushing his hair and
teeth. He performed simple calculations accu-
rately but was unable to perform two-part com-
mands; he was slow when he spelled “table” and
“world” backward and when he counted down
from 100 in increments of 7. He could not pro-
vide abstract explanations for proverbs.
Examination of the function of cranial nerves
II through XII revealed left-eye ptosis, a finding
that was also visible on the patient’s driver’s Figure 1. Clinical Photographs of Skin Lesions.
license photograph, which had been taken in the Panel A shows a purple-brown scaly papule (0.5 cm in
remote past. There was intermittent twitching diameter) on the medial left knee, and Panel B shows a
on the right side of the face. Pronator drift was nonblanching purple-brown patch (1.5 cm in diameter)
on the medial aspect of the left palmar foot. Photographs
present on the right side of the body; the motor
courtesy of Dr. Alvin Das.
examination was otherwise normal, as were ex-
aminations of sensation and deep-tendon reflex-
es. Finger–nose–finger movements were smooth
and accurate bilaterally after the patient under- The red-cell indexes, anion gap, and results of
stood the task. The stance and stride were nor- renal-function tests were normal, as were blood
mal, but the patient walked slowly and was un- levels of calcium, phosphorus, magnesium, aspar-
able to walk with a tandem gait or on his toes tate aminotransferase, alanine aminotransferase,
or heels. The Romberg test was negative. alkaline phosphatase, total bilirubin, direct bili-
Examination of the skin revealed a purple- rubin, vitamin B12, and thyrotropin. Urinalysis
brown scaly papule (0.5 cm in diameter) on the showed 1+ leukocyte esterase, 1+ bacteria, a pH
medial left knee (Fig. 1A), a nonblanching purple- of 6.0, and a specific gravity of 1.014; there were
brown patch (1.5 cm in diameter) on the medial 3 to 5 red cells and 10 to 20 white cells per high-
aspect of the left palmar foot (Fig. 1B), and power field. Urine and blood toxicology screens
purple macules on the hard and soft palates. were negative. Other laboratory test results are
There were also multiple erythematous scars, shown in Table 1.
including one on the left arm with an area of Dr. R. Gilberto Gonzalez: Computed tomography
hard scale at the periphery; a red plaque (3 cm of the head revealed ill-defined hypodensities in
in diameter) on the chest with heaped-up central the white matter of the frontal lobes, which ex-
scale, hemorrhagic crust, and purulent discharge; tended into the genu of the corpus callosum,
a red plaque (4 cm in diameter) on the left flank and in the posterior periventricular white matter
with focal areas of scale and brown crust; gritty (Fig. 2A). There was also an extraaxial calcifica-
papules on the face; a large scaly red plaque on tion (4 cm in diameter) overlying the right fron-
the back; and flaky scale on the scalp. The re- tal lobe that was thought to possibly represent a
mainder of the physical examination was normal. partially calcified meningioma (Fig. 2B).
n engl j med 376;26 nejm.org June 29, 2017 2581

Table 1. Laboratory Data. A
Reference Range,
Variable Adults* On Presentation
Hematocrit (%) 41.0–53.0 27.7
Hemoglobin (g/dl) 13.5–17.5 9.7
White‑cell count (per mm3) 4500–11,000 3130
Differential count (%)
Neutrophils 40–70 60.4
Lymphocytes 22–44 28.4
Monocytes 4–11 8.3
Eosinophils 0–8 1.6
Basophils 0–3 0.3
Platelet count (per mm3) 150,000–400,000 132,000
Sodium (mmol/liter) 135–145 132
Potassium (mmol/liter) 3.4–5.0 3.2
Chloride (mmol/liter) 98–108 98
Carbon dioxide (mmol/liter) 23–32 23
Glucose (mg/dl)† 70–110 121
Protein (g/dl)
Total 6.0–8.3 9.1
Albumin 3.3–5.0 3.7 B
Globulin 1.9–4.1 5.4
Lipase (U/liter) 13–60 136
* Reference values are affected by many variables, including the patient popula‑
tion and the laboratory methods used. The ranges used at Massachusetts
General Hospital are for adults who are not pregnant and do not have medi‑
cal conditions that could affect the results. They may therefore not be appro‑
priate for all patients.
† To convert the values for glucose to millimoles per liter, multiply by 0.05551.
Dr. Goldstein: Six hours after the patient arrived

in the emergency department, he had a 2-minute
episode of aphasia. The temperature was 38.2°C.
Ceftriaxone, vancomycin, acyclovir, and leveti-
racetam were administered intravenously, and
additional imaging studies were obtained.
Dr. Gonzalez: Magnetic resonance imaging (MRI)
of the head was performed with and without the
administration of intravenous contrast material Figure 2. CT Scan of the Head.
(Fig. 3). T2-weighted images showed an abnor- An axial image obtained at the level of the lateral ven‑
mal hyperintense signal in the frontoparietal tricles shows abnormal hypodensities that involve the
subcortical and deep white matter and most prominent‑
white matter that was slightly more prominent
ly involve the frontal lobes (Panel A). A coronal image
in the right frontal lobe than in the left frontal shows an extraaxial calcified mass adjacent to the right
lobe and that extended into the genu of the cor- frontal lobe that most likely represents a calcified menin‑
pus callosum; there was no local mass effect or gioma (Panel B, arrow).
abnormal restricted diffusion. There was also a

Figure 3. MRI of the Head. A

An axial fluid‑attenuated inversion recovery image ob‑
tained at the level of the lateral ventricles shows abnor‑
mal increased signal in the subcortical and deep white
matter that predominantly involves the frontal lobes
(Panel A). These abnormalities correspond to those seen
on the CT scan. An axial, contrast‑enhanced, T1‑weighted
image obtained at the level of the lateral ventricles shows
no abnormal contrast enhancement (Panel B).
small exophytic hypointense lesion along the in-

ner table of the right frontal bone that was sug-
gestive of a small calcified meningioma, as well
as mild bilateral prominence of the parotid
glands, which had restricted diffusion.
Dr. Goldstein: After the MRI, the patient had
another 2-minute witnessed episode, during
which he was staring, twitching, and unable to
speak; afterward, he seemed to be more con-
fused than he had been previously. A lumbar
puncture was performed. The opening pressure
was 9 cm of water, and the cerebrospinal fluid
(CSF) was clear and colorless, without xantho-
chromia. Examination of the CSF revealed 4 red
cells and 7 white cells per microliter, a white-cell B
differential count of 80% lymphocytes and 20%
monocytes, a protein level of 97 mg per deciliter
(reference range, 5 to 55), and a glucose level of
53 mg per deciliter (2.9 mmol per liter [reference
range, 50 to 75 mg per deciliter; 2.8 to 4.2 mmol
per liter]). Gram’s staining revealed moderate
mononuclear cells, very rare polymorphonuclear
leukocytes, and no organisms.
The patient was admitted to the hospital. On
examination, there was tender inguinal lymph-
adenopathy on the left side. Diagnostic tests
were performed.
Differ en t i a l Di agnosis
Dr. Shibani S. Mukerji: In formulating the differen-
tial diagnosis in this case, the first step is to
determine the immune status of this patient. We
know that he is a 48-year-old man who presented
with confusion, weight loss, lymphadenopathy,
pancytopenia, and purplish skin lesions. When
considering these findings in the context of high-
risk sexual behavior, it is reasonable to conclude
that he most likely has undiagnosed, advanced
acquired immunodeficiency syndrome (AIDS),

particularly because the skin lesions are sugges- Metabolic and Toxic Disorders
tive of Kaposi’s sarcoma. If we assume that he Many confusional syndromes are caused by toxic
has AIDS, what disease processes would lead to or metabolic abnormalities. Clinical findings may
hyperactive agitation, encephalopathy, subtle motor include tremor and asterixis. Wernicke’s encepha-
deficits, gait impairment, and seizures? lopathy due to a vitamin B1 (thiamine) deficiency
can occur in the context of moderate alcohol
Primary Psychiatric Disorders consumption and a diet low in added sugar and
Is this patient’s presentation consistent with a potentially other nutrients. However, Wernicke’s
psychiatric disorder? The presenting symptoms encephalopathy is characterized by global confu-
contrast strikingly with the findings on exami- sion, which was absent in this patient, and the
nation. Although the patient had symptoms of typical accompanying features of nystagmus,
mania, agitation, disinhibition, and possible cerebellar dysfunction, and ocular palsies were
apathy to self-appearance, his neurologic exami- also absent. Another nutritional deficiency that
nation did not show evidence of mania. He had is associated with features of dementia or psy-
no evidence of visual or auditory hallucinations, chosis is vitamin B12 (cobalamin) deficiency. Vita-
his thinking was not tangential, and he engaged min B12 is required for the maintenance of
with the examiner in a logical manner; these myelinated fibers,2 and a deficiency is typically
findings suggest that the underlying illness is manifested by visual impairment, sensory defi-
unlikely to be primary psychosis. Instead, he cits, or focal motor deficits. The vitamin B12 level
perseverated when speaking and had difficulty was normal in this patient, and neurologic symp-
following two-step instructions, slowness when toms that are commonly suggestive of this diag-
he spelled simple words and performed tasks, nosis were absent.
and rigidity of thought. He also had gait insta- Fulminant encephalopathy, which is often ac-
bility with marked slowness that could not be companied by seizures, can occur in persons with
explained by weakness or spasticity. He did not HIV-1 infection who use cocaine, heroin, or both.
have elementary focal neurologic signs, such as T2-weighted images show diffuse hyperintense
hemiplegia, visual deficit, sensory deficit, or ab- lesions in the basal ganglia.3 Patients with this
normal reflexes; however, he did have pronation form of encephalopathy have uncontrolled HIV-1
of the right arm with no weakness, as well as infection; 80% have renal failure, and the me-
persistent movement on the right side of the face dian survival is reported to be 21 days despite
that was highly suggestive of epilepsia partialis supportive therapy.3 The negative toxicology
continua and ultimately culminated in episodes screens and incongruent findings on imaging in
of aphasia and confusion that were suggestive of this patient make this diagnosis unlikely.
focal seizures.
This patient’s presentation is reminiscent of Cancers of the CNS
early descriptions of patients with AIDS that On the basis of this patient’s age, his likely diag-
arose when it became apparent that advanced nosis of HIV-1 infection, and his clinical presen-
human immunodeficiency virus type 1 (HIV-1) tation, primary CNS lymphoma should be a strong
infection could be complicated by a dementing consideration. Primary CNS lymphoma can in-
neurologic disorder.1 Could this patient have a volve the frontal lobes or their white-matter
subacute, progressive dementing illness due to connections to subcortical tissue, and it is con-
HIV-1 infection with direct involvement of the sistently associated with Epstein–Barr virus in
central nervous system (CNS)? Although the persons with AIDS. The peak incidence is during
features of the patient’s presentation are con- the fourth decade of life in persons with HIV-1
sistent with a dementing illness that is due to infection. High-grade glioma can also involve
HIV-1 infection, the principle of medical parsi- both frontal lobes and infiltrate the corpus cal-
mony rarely applies in patients with AIDS. There- losum, and thus it represents another possibility
fore, a broad differential diagnosis must be in this case. Cutaneous Kaposi’s sarcoma with
considered that includes toxic and metabolic con- metastasis to the brain is another consideration,
ditions, cancer, and other causes of infectious and a blood CD4 count of less than 200 cells per
encephalitis. cubic millimeter at the time of diagnosis is a

poor prognostic factor. However, despite the pro- be phenotypically similar to HIV-1 encephalopa-
found dysfunction in the frontal lobe, this pa- thy, and a subset of affected patients present with
tient did not have the neurologic deficits (i.e., cranial-nerve deficits. A polymerase-chain-reac-
weakness or sensory abnormalities, frontal re- tion (PCR) assay for cytomegalovirus DNA and
lease signs, or visual deficits) that would be ex- an ophthalmologic examination for cytomegalo-
pected in a patient with these cancers. In addition, virus retinitis should be performed; however,
among patients with primary CNS lymphoma given the absence of focal neurologic findings
or glioma or tumor metastasis to the brain, T2- and the presence of imaging findings suggestive
weighted images typically show hyperintense of widespread demyelinating disease, cytomega-
lesions with contrast enhancement, diffusion lovirus encephalitis does not account for all the
restriction, and mass effect; the absence of these features of this patient’s presentation.
findings in this patient argues against these di-
agnoses. The meningioma identified on the im- Progressive Multifocal Leukoencephalopathy
aging studies has benign characteristics and is Progressive multifocal leukoencephalopathy is a
not the cause of this clinical presentation. demyelinating disease of the CNS that is caused
by the human polyomavirus JC virus.5 Classic pro-
Infection gressive multifocal leukoencephalopathy typically
Infectious encephalitis is a major concern in per- results in neurologic deficits, including hemipa-
sons who have suspected advanced immunosup- resis, sensory deficits, and aphasia, and up to 18%
pression due to HIV-1 infection. Patients with of affected patients have seizures.6 Lesions are
either toxoplasmosis or bacterial brain abscesses typically well demarcated, diffuse, and located
who present with seizures typically have focal primarily in subcortical white matter; they may
neurologic deficits; however, it is unlikely that involve the corpus callosum and have no mass
these infections would be restricted to the fron- effect. Although contrast enhancement is uncom-
tal lobe and thus it is unlikely that either infec- monly seen in patients with progressive multifo-
tion would account for the clinical presentation cal leukoencephalopathy, it has been reported in
in this case. Herpes simplex virus is a common patients with HIV-1 infection who have received
cause of sporadic encephalitis that is associated treatment with antiretroviral therapy. Nonclassic
with behavioral disturbances and seizures. Al- forms of progressive multifocal leukoencepha-
though testing for herpes simplex virus is crucial lopathy include JC virus granule-cell neuronop-
in this case, given the availability of antiviral athy, which leads to productive infection of
therapy, the changes in the subcortical white cerebellar granule-cell neurons, and JC virus en-
matter in the absence of hyperintense lesions in cephalopathy, which leads to productive infec-
the medial temporal lobes on MRI make this tion of cortical pyramidal neurons; however, the
diagnosis unlikely. Varicella–zoster virus leuko- clinical description and imaging findings in this
encephalitis is a rare opportunistic infection that case do not fit either of these diagnoses.5 Classic
occurs in patients with HIV-1 infection; it is asso- progressive multifocal leukoencephalopathy re-
ciated with confusion and with multifocal, nec- mains a consideration in this patient, although
rotizing white-matter lesions on MRI.4 Although the diagnosis would necessitate visualization of
the skin lesions described in this case are not characteristic imaging findings and detection of
consistent with disseminated varicella–zoster JC virus DNA in the CSF by means of PCR assay.
virus, a rash is not required to make the diagno-
sis. Persons with varicella–zoster virus leukoen- HIV-1 Encephalopathy and Encephalitis
cephalitis typically have ataxia, visual impairment, Viral entry into the CNS occurs early after pri-
hemiparesis, or sensory changes, and these find- mary HIV-1 infection and, in the absence of
ings were absent in this patient. Cytomegalovi- treatment, can result in a fulminant dementing
rus encephalitis is an important consideration, illness that is marked by psychomotor retarda-
especially in patients with a blood CD4 count of tion and seizures.7 This syndrome is commonly
less than 50 cells per cubic millimeter. Clinical referred to as HIV-1 encephalopathy (also known
features of cytomegalovirus encephalitis include as HIV-1–associated dementia). The neuropatho-
progressive nonfocal encephalopathy, which can logical correlate is HIV-1 encephalitis, which is

characterized by multinucleated giant cells, dif- and they recommended that testing for HIV anti-
fuse microgliosis, and glial scarring.8 In contrast bodies be performed and a CD4 T-lymphocyte
to the imaging findings in patients with progres- count be obtained. Meanwhile, the results of
sive multifocal leukoencephalopathy, T2-weighted neuroimaging were interpreted in the context of
images in patients with HIV-1 encephalopathy presumed HIV-1 infection. Both HIV-1 encepha-
show hyperintense lesions in subcortical white lopathy and progressive multifocal leukoenceph-
matter, and gray-matter involvement (including alopathy were considered; although we struggled
involvement of subcortical structures, such as the to differentiate between these diagnoses, we
basal ganglia) has been described. In this patient, thought that the patient’s history and imaging
CSF analysis revealed a minimally elevated white- findings were most consistent with HIV-1 en-
cell count with lymphocytic predominance and cephalopathy.
an elevated protein level; these findings are seen
in untreated patients with HIV-1 encephalopathy Cl inic a l Di agnosis
but are not specific for the diagnosis. Cortical
atrophy can be present at later stages, whereas Advanced human immunodeficiency virus type 1
contrast enhancement is almost always absent. (HIV-1) infection complicated by Kaposi’s sar-
coma and HIV-1 encephalopathy.
Summary
This patient had systemic symptoms that are Dr . Shib a ni S . Muk erji’s
suggestive of AIDS and had subcortical cognitive Di agnosis
dysfunction, hypokinetic motor abnormalities,
gait impairment, and seizures, as well as an ab- Human immunodeficiency virus type 1 (HIV-1)
sence of elementary neurologic findings despite encephalopathy in a patient with acquired im-
widespread, ill-defined, bilateral, largely sym- munodeficiency syndrome (AIDS).
metric hyperintensities in subcortical white mat-
ter on T2-weighted imaging; these findings lead Pathol o gic a l Discussion
me to suspect a primary neurologic diagnosis of
HIV-1 encephalopathy. Encephalopathy that is Dr. Goldstein: A fourth-generation test for HIV
associated with untreated HIV-1 infection and antigen and antibody was positive, and the re-
occurs in the absence of opportunistic infections sults of a supplemental Western blot assay con-
typically results in steadily progressive neuro- firmed the diagnosis of HIV-1 infection. The
logic deterioration, although some patients have plasma HIV-1 RNA viral load was 426,000 copies
an abrupt acceleration in decline. In order to per milliliter, and the blood CD4 count was
establish this diagnosis, I would recommend 64 cells per cubic millimeter. The CSF HIV-1
testing for HIV-1 antibodies; if the testing is RNA viral load was 238,000 copies per milliliter.
positive, I would obtain a CD4 T-lymphocyte Tests were negative for JC virus, cytomegalovirus,
count and measure the HIV-1 RNA viral load in Epstein–Barr virus, herpes simplex virus, varicella–
the blood and CSF. Because this patient had re- zoster virus, cryptococcosis, toxoplasmosis, tuber-
portedly been in a normal state 2 weeks before culosis, and syphilis.
this presentation, I am uncertain about whether Dr. Stefan Kraft: Biopsies of lesions on the chest,
HIV-1 encephalopathy is the sole diagnosis; con- knee, and foot were performed. Examination of
firmation of the diagnosis requires that we rule the chest-biopsy specimen revealed classic fea-
out other infectious causes, most importantly tures of a nodular basal-cell carcinoma. Similar
infection with cytomegalovirus and JC virus. to other nonmelanoma skin cancers, basal-cell
Dr. Virginia M. Pierce (Pathology): Dr. Goldstein, carcinomas occur at rates that are moderately
what was your impression when you evaluated higher than average among persons with HIV-1
this patient? infection.9
Dr. Goldstein: In the emergency department, the Examination of the knee-biopsy specimen
neurology consultant noted the purplish skin revealed dermal fibrosis, chronic inflammation,
lesions and suspected Kaposi’s sarcoma and ad- and subtle spindle-cell proliferation (Fig. 4A).
vanced immunosuppression due to HIV-1 infec- The spindle cells had cytologic atypia with en-
tion. The infectious disease team was consulted, larged hyperchromatic nuclei (Fig. 4B). Examina-

A B
C D
Figure 4. Skin-Biopsy Specimens.

Hematoxylin and eosin staining of the knee‑biopsy specimen (Panel A) shows dermal fibrosis, chronic inflammation,
and subtle spindle‑cell proliferation. At higher magnification (Panel B), the spindle cells show cytologic atypia with
enlarged hyperchromatic nuclei (arrows). Hematoxylin and eosin staining of the foot‑biopsy specimen (Panel C)
shows dermal fibrosis, chronic inflammation, and subtle spindle‑cell proliferation with extension into the eccrine
glands. At higher magnification (Panel D), hemorrhage (black arrow), hemosiderin deposition (arrowheads), and ill‑
defined slitlike vessels (white arrow) are seen. An immunohistochemical stain of the foot‑biopsy specimen for human
herpesvirus 8 (Panel E) shows nuclear staining, a finding that confirms the diagnosis of Kaposi’s sarcoma.

tion of the foot-biopsy specimen revealed similar In choosing an antiretroviral regimen for a
findings, except that the spindle-cell prolifera- patient with HIV-1 encephalopathy, some experts
tion extended deeper into the dermis and into recommend the use of medications with high
the eccrine glands (Fig. 4C). On closer examina- CNS penetration. Factors that influence drug
tion, the infiltrative spindle-cell proliferation had penetration include molecular weight, protein
foci of hemorrhage, hemosiderin deposition, and binding, lipophilicity, and transporter interac-
occasional ill-defined slitlike vessels, findings sug- tions; these factors are used to assess the effec-
gestive of an atypical vascular neoplasm (Fig. 4D). tiveness score for CNS penetration.15 However,
To confirm the vascular nature of the neoplasm, there is controversy about whether antiretroviral
immunohistochemical staining with anti-CD34 drugs with higher CNS penetration are more ef-
antibodies was performed, and both the knee- fective in improving neurocognitive function.16
and foot-biopsy specimens showed positive stain- The antiretroviral regimen chosen for this pa-
ing in dermal spindle cells and ill-defined ves- tient was a combination of dolutegravir with a
sels. Given the presence of an atypical vascular fixed-dose formulation of tenofovir and emtric-
neoplasm that predominantly consisted of infil- itabine; this regimen is associated with few side
trative spindle cells, Kaposi’s sarcoma was sus- effects and is taken once daily (which may facili-
pected. Human herpesvirus 8 is found in all tate adherence), and dolutegravir has high CNS
forms of Kaposi’s sarcoma, and in the majority penetration.
of cases, it can be detected by means of immu- This patient’s presentation with dementia is a
nohistochemical staining.10 Immunohistochemi- reminder that HIV-1 infection is still being diag-
cal staining with anti–human herpesvirus 8 anti- nosed too late in the course of disease.17 Patients
bodies was performed, and both the knee- and with ongoing risks should be tested at least an-
foot-biopsy specimens showed positive nuclear nually, and high-risk patients should undergo re-
staining in the spindle cells (Fig. 4E), a finding peat testing every 3 to 6 months. Earlier diagno-
that confirmed the presence of Kaposi’s sarcoma. sis and treatment can prevent the development of
life-altering complications, such as the devastating
neurocognitive impairment seen in this patient.18
Discussion of M a nagemen t
Dr. Pierce: Dr. Goldstein, how is the patient
Dr. Rajesh T. Gandhi: Acute HIV-1 infection typi- doing now?
cally involves the CNS.11 Although CNS involve- Dr. Goldstein: Antiretroviral therapy was started
ment is usually asymptomatic, some patients on the first hospital day. The patient’s hospital-
with primary HIV-1 infection present with signs ization was complicated by impulsive and ag-
and symptoms of meningitis, encephalitis, the gressive behavior and lack of insight into his
Guillain–Barré syndrome, or other neurologic disease. He attempted elopement repeatedly and
complications. If HIV-1 is unrecognized and un- was discharged to a secure facility after 6 weeks.
treated (as in this patient), it may cause neuronal There, his condition initially improved and he ad-
damage and result in HIV-1–associated neuro- hered to the antiretroviral therapy; he was dis-
cognitive disorders, including the most severe charged home after 2 weeks. During a follow-up
form, HIV-1 encephalopathy.12 clinic visit, his family noted that he continued to
The primary treatment for this patient is anti- have impulsive behavior. Readmission to the
retroviral therapy. Since the introduction of ef- hospital was offered, but the patient refused.
fective antiretroviral therapy, there has been a One month later, MRI of the head showed pro-
marked decrease in the incidence of HIV-1 en- gression of his neurologic disease. He again re-
cephalopathy.13 However, despite the decreased fused admission and has been lost to follow-up.
rate of dementia, less severe manifestations of
HIV-1–associated neurocognitive disorders have Fina l Di agnose s
not decreased in frequency; this phenomenon is
referred to as the therapeutic paradox. As a re- Advanced acquired immunodeficiency syndrome
14
sult, HIV-1–associated neurocognitive disorders (AIDS) complicated by human immunodeficiency

continue to be an important problem that affects virus type 1 (HIV-1) encephalopathy.
daily functions, quality of life, and adherence to Basal-cell carcinoma.
antiretroviral therapy among affected patients. Kaposi’s sarcoma.

This case was presented at the 10th Annual Workshop on Ad- the Centre for the Aids Programme of Research in South Africa,
vanced Clinical Care–AIDS in Durban, South Africa, organized by the University of KwaZulu-Natal, the South African HIV Clini-
Drs. Henry Sunpath and Mahomed-Yunus S. Moosa (Infectious cians Society, and the KwaZulu-Natal Department of Health.
Diseases Unit, Nelson R. Mandela School of Medicine, University Disclosure forms provided by the authors are available with
of KwaZulu-Natal) and Dr. Rajesh T. Gandhi (Massachusetts Gen- the full text of this article at NEJM.org.
eral Hospital and the Ragon Institute) and sponsored by the Har- We thank Dr. Nagagopal Venna for helpful discussions about
vard University Center for AIDS Research (NIH P30 AI060354), the case.
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Case 20-2017: A 48-Year-Old Man With Weight Loss, Confusion, Skin Lesions, and Pancytopenia

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Case 20-2017: A 48-Year-Old Man With Weight Loss, Confusion, Skin Lesions, and Pancytopenia

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The n e w e ng l a n d j o u r na l of m e dic i n e

Case Records of the Massachusetts General Hospital

Founded by Richard C. Cabot

Case 20-2017: A 48-Year-Old Man

Pr e sen tat ion of C a se

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The New England Journal of Medicine

On examination, the patient appeared thin A

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Table 1. Laboratory Data. A

Dr. Goldstein: Six hours after the patient arrived

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Figure 3. MRI of the Head. A

small exophytic hypointense lesion along the in-

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The New England Journal of Medicine

Figure 4. Skin-Biopsy Specimens.

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sult, HIV-1–associated neurocognitive disorders (AIDS) complicated by human immunodeficiency

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The New England Journal of Medicine

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