nejmcpc2211356

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

Eric S. Rosenberg, M.D., Editor
David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Kathy M. Tran, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Emily K. McDonald, Tara Corpuz, Production Editors
Case 9-2023: A 20-Year-Old Man

with Shortness of Breath and Proteinuria
Shaun F. Fitzgerald, M.D., M.P.H., Teresa Victoria, M.D., Ph.D.,
Weizhen Tan, M.D., and Cynthia K. Harris, M.D.
Pr e sen tat ion of C a se
Dr. Miranda M. Ravicz (Pediatrics): A 20-year-old man with bipolar disorder was From the Departments of Pediatrics
transferred to this hospital because of hemoptysis and hypoxemia. (S.F.F., W.T.), Radiology (T.V.), and Pa
thology (C.K.H.), Massachusetts General
Eleven months before the current presentation, the patient received a diagnosis Hospital, and the Departments of Pedi
of bipolar disorder. Six weeks before the current presentation, he was taken to atrics (S.F.F., W.T.), Radiology (T.V.), and
another hospital for evaluation of racing thoughts, generalized hyperactivity, and Pathology (C.K.H.), Harvard Medical
School — both in Boston.
difficulty sleeping. He was admitted to a psychiatric hospital for treatment. During
the admission, the patient was involved in an altercation and was struck on the N Engl J Med 2023;388:1127-35.
DOI: 10.1056/NEJMcpc2211356
left side of the chest; pain subsequently developed in that area. Five weeks before Copyright © 2023 Massachusetts Medical Society.
the current presentation, chest pain persisted, and nausea, vomiting, and de-
creased appetite developed. The patient was transported from the psychiatric
hospital to the emergency department of the other hospital for evaluation. Imag-
ing studies were obtained.
Dr. Teresa Victoria: Computed tomography (CT) of the chest (Fig. 1A) revealed
ground-glass opacities in the left lower lobe.
Dr. Ravicz: The patient was told that he had a pulmonary contusion and was
transported back to the psychiatric hospital. The dosages of quetiapine and pali-
peridone were increased. Four weeks before the current presentation, the patient
had urticaria and intermittent nausea; a single dose of methylprednisolone was
administered. Three weeks before the current presentation, the patient was dis-
charged home.
Ten days before the current presentation, chest pain continued, cough devel-
oped, and nausea increased in severity. The patient was evaluated in the emer-
gency department of a second hospital. Imaging studies were obtained.
Dr. Victoria: Radiography of the chest (Fig. 1B) revealed a consolidation in the
left lower lobe and a left pleural effusion.
Dr. Ravicz: A course of doxycycline was started for the treatment of presumed
pneumonia, and the patient was discharged home. During the subsequent 6 days,
the cough and chest pain abated. Four days before the current presentation, the
course of doxycycline was completed. During the next several days, the cough in-
creased in severity and became productive of yellow sputum with dark-red streaks,
n engl j med 388;12 nejm.org March 23, 2023 1127

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A
fluenza A and B viruses, respiratory syncytial vi-
rus, and severe acute respiratory syndrome coro-
navirus 2. Other laboratory test results are shown
in Table 1. Blood was obtained for culture, and
additional imaging studies were obtained.
Dr. Victoria: CT angiography of the chest, per-
formed after the administration of intravenous
contrast material, revealed emboli of the right
and left pulmonary arteries that extended into
multiple segmental and subsegmental branches
(Fig. 2). There were wedge-shaped opacities with-
B out enhancement in the left upper and lower
lobes, findings consistent with infarction. There
were small pleural effusions that were larger on
the left side than on the right side.
Dr. Ravicz: Treatment with enoxaparin, vanco-
mycin, and cefepime was started, and intrave-
nous fluids were administered. The patient was
admitted to the second hospital. On hospital day 2,
the oxygen saturation decreased, and supple-
mental oxygen was administered through a nasal
cannula. Blood cultures showed no growth. The
patient was transferred to this hospital for ad-
ditional evaluation and treatment.
On admission to this hospital, additional his-
tory was obtained. The chest pain, cough, hemop-
tysis, shortness of breath, and nausea continued.
Figure 1. Initial Imaging Studies.
The patient reported fatigue and weight loss that
A chest CT image obtained at the first hospital 5 weeks
before the current presentation (Panel A) shows ground
had started after the injury to the chest. He had
glass opacities in the left lower lobe (arrow). A chest also noticed discoloration in his fingers that was
radiograph obtained at the second hospital 10 days associated with changes in temperature. There
before the current presentation (Panel B) shows a was no headache, abdominal pain, or joint pain.
consolidation in the left lower lobe and an associated The patient had a history of asthma, migraines,
moderatesized pleural effusion (arrow).
and attention deficit–hyperactivity disorder. Bi-
polar disorder had been diagnosed when he was
and shortness of breath developed; nausea also hospitalized for mania, grandiose thoughts, and
increased in severity. One day before the current paranoid delusions. Medications included queti-
presentation, the patient was evaluated again in apine, paliperidone, and methylphenidate. Sulfa
the emergency department of the second hospital. drugs and valproate had caused rash, nausea,
On evaluation, the patient appeared ill and and vomiting. The patient had previously been
had difficulty breathing. The temporal tempera- sexually active with female partners. He drank
ture was 37.5°C, the blood pressure 99/50 mm Hg, alcohol rarely and vaped marijuana frequently;
the heart rate 127 beats per minute, the respira- he did not smoke tobacco or use illicit drugs.
tory rate 31 breaths per minute, and the oxygen His mother, maternal aunt, paternal aunt, and
saturation 95% while the patient was breathing paternal uncle had depression.
ambient air. The hemoglobin level was 11.3 g On examination, the temperature was 38.6°C,
per deciliter (reference range, 14.0 to 18.0) and the blood pressure 89/40 mm Hg, the heart rate
the albumin level 1.3 g per deciliter (reference 121 beats per minute, the respiratory rate 20
range, 3.4 to 5.0). Blood levels of electrolytes and breaths per minute, and the oxygen saturation
glucose were normal, as were the results of liver- 98% while the patient was receiving supplemen-
function tests. Nucleic acid amplification testing tal oxygen through a nasal cannula at a rate of
of a nasopharyngeal swab was negative for in- 2 liters per minute. The right lung was clear on
1128 n engl j med 388;12 nejm.org March 23, 2023

Case Records of the Massachuset ts Gener al Hospital
Table 1. Laboratory Data.*
Reference Range, On Admission, Reference Range, On Admission,

Variable Second Hospital Second Hospital This Hospital† This Hospital
Blood
Hemoglobin (g/dl) 14.0–18.0 11.3 12.0–16.0 8.7
Hematocrit (%) 42.0–52.0 35.2 36.0–46.0 26.3
White-cell count (per μl) 4500–11,000 9500 4500–11,000 7310
Differential count (per μl)
Neutrophils 1800–7700 7590 1800–7700 5940
Lymphocytes 900–5400 1270 1000–4800 710
Monocytes 100–1100 550 200–1200 420
Eosinophils 0–800 0 0–900 190
Basophils 0–200 10 0–300 20
Platelet count (per μl) 150,000–450,000 296,000 150,000–400,000 213,000
Urea nitrogen (mg/dl) 8–25 13 8–25 13
Creatinine (mg/dl) 0.50–1.14 1.14 0.60–1.50 0.98
Lactic acid (mmol/liter) 0.4–2.0 1.1 0.5–2.0 0.6
Albumin (g/dl) 3.4–5.0 1.3 3.4–5.0 1.6
Globulin (g/dl) 2.0–3.5 4.7 2.0–3.5 3.4
Urine
Bilirubin — — Negative Negative
Blood — — Negative 2+
Glucose — — Negative Negative
Ketones — — Negative Negative
Leukocyte esterase — — Negative Negative
Nitrites — — Negative Negative
Protein — — Negative 3+
Red cells (per high-power field) — — 0–2 5–10
White cells (per high-power field) — — 0–2 3–5
Hyaline casts (per high-power field) — — 0–2 10–20
* To convert the values for urea nitrogen to millimoles per liter, multiply by 0.357. To convert the values for creatinine to
micromoles per liter, multiply by 88.4. To convert the values for lactic acid to milligrams per deciliter, divide by 0.11110.
† Reference values are affected by many variables, including the patient population and the laboratory methods used. The
ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical condi
tions that could affect the results. They may therefore not be appropriate for all patients.
auscultation, but the left lung had diminished Differ en t i a l Di agnosis

sounds. There was no abdominal tenderness,
joint swelling, or rash. The patient had a flat af- Dr. Shaun F. Fitzgerald: This 20-year-old man who
fect, apathy, grandiose thoughts, poverty of speech had recently received a diagnosis of bipolar dis-
and thought, and psychomotor retardation. There order was evaluated for chest pain after trauma
was no evidence of paranoia or hallucinations. to the chest wall. Chest CT revealed ground-
The hemoglobin level was 8.7 g per deciliter and glass opacities; this finding is nonspecific, with
the albumin level 1.6 g per deciliter. Urinalysis possible causes including infectious processes,
revealed 2+ blood and 3+ protein; other labora- chronic interstitial lung disease, and acute alveo-
tory test results are shown in Table 1. lar disease. Although the differential diagnosis
Diagnostic tests were performed. associated with this finding is broad, the initial

A B
C D
Figure 2. Imaging Studies Obtained on Current Presentation.

A coronal image (Panel A) and an axial image (Panel B) from CT angiography of the chest show large emboli of the
central right and left pulmonary arteries (Panels A and B, respectively; arrows) that extend to multiple segmental
and subsegmental branches. Small pleural effusions are present in both lungs. An additional axial image (Panel C)
shows a wedgeshaped infarct in the left lower lobe (arrow); a similar infarct was also observed in the left upper
lobe (not shown). A perfusion image (Panel D) shows heterogeneous perfusion in both lungs (arrowhead) and a
lack of perfusion associated with the bilateral pleural effusions and with the infarct in the left lower lobe (arrow).
diagnosis of pulmonary contusion was appropri- in the lungs and the kidneys are related. There-
ate, given the history of trauma with few other fore, I will focus on diseases that cause glomeru-
symptoms present. lonephritis and pulmonary disease.
However, during the next several weeks, short-
ness of breath and cough with hemoptysis devel- Infective Endocarditis
oped. The evolution of the patient’s respiratory Patients with infective endocarditis involving
symptoms and his subsequent imaging findings, the right side of the heart can have pulmonary
including pulmonary embolism with pulmonary emboli that originated from the tricuspid valve.
infarction, are more consistent with systemic dis- In addition, patients with infective endocardi-
ease. In addition, the patient was found to have tis can have glomerulonephritis that is caused
hypoalbuminemia, proteinuria, microscopic he- by circulating immune complexes. This patient
maturia, and an active urinary sediment with had fever on presentation to this hospital,
red cells and white cells. Although the presence which could be indicative of infection. How-
of hypoalbuminemia may suggest the possibility ever, he did not have any specific risk factors
of nephrotic syndrome, the absence of edema on for infective endocarditis or have a heart mur-
physical examination makes nephrotic syndrome mur or other examination findings associated
less likely. The active urinary sediment is sug- with this condition. The absence of these
gestive of glomerulonephritis. findings and the negative blood cultures make
In developing a differential diagnosis for this a diagnosis of infective endocarditis unlikely
patient, I will assume that the disease processes in this case.

Poststreptococcal Glomerulonephritis served in patients with EGPA. In addition, there

This patient had presumed pneumonia, and his was no eosinophilia. Although the results of
symptoms improved with the use of doxycycline. ANCA testing are not available, EGPA is unlikely
Could his renal process be explained by post- to explain his presentation.
streptococcal glomerulonephritis? Group A strep- The patient did have several symptoms and
tococcus can cause community-acquired pneu- signs that were consistent with GPA and MPA,
monia, but it is not a common cause, and including cough, dyspnea, and chest pain, as
poststreptococcal glomerulonephritis is most well as proteinuria and hematuria. In addition,
likely to occur after pharyngitis or a skin or soft- patients with ANCA-associated vasculitis have
tissue infection due to group A streptococcus. an increased incidence of deep venous thrombo-
The absence of a documented antecedent group sis, which could explain his pulmonary embo-
A streptococcal infection makes a diagnosis of lism.2 However, GPA and MPA would not be as-
poststreptococcal glomerulonephritis unlikely, sociated with normal renal function, and both of
as does the absence of acute kidney injury. these conditions typically develop in older adults.
GPA and MPA remain possible diagnoses; re-
IgA Nephropathy or Henoch–Schönlein sults of ANCA testing would be informative.
Purpura Nephritis
Patients with IgA nephropathy usually present Anti-GBM Disease
with hematuria and evidence of an antecedent or Anti–glomerular basement membrane (anti-GBM)
concurrent upper respiratory infection. In this disease can also cause pulmonary and renal
patient, ground-glass opacities had been noted disease. Circulating anti-GBM antibodies pro-
on chest CT before his presentation with micro- duce pulmonary symptoms only after disruption
scopic hematuria and subsequent cough. How- of the alveolar endothelium occurs and the anti-
ever, he did not have rhinitis, sore throat, or bodies are permitted to access the alveolar base-
malaise, which are typical symptoms of upper ment membrane; thereafter, the inflammatory
respiratory infection. There were no previous response mediates damage and disease. It is in-
episodes of hematuria, and such episodes might triguing that this patient’s symptoms began after
be expected with IgA nephropathy. Likewise, trauma to the chest wall, which could have
there was no joint or abdominal pain, and such caused injury to the alveolar endothelium. The
pain would be suggestive of Henoch–Schönlein history of vaping and recent episode of pneumo-
purpura. The progression of his respiratory nia are also potential risk factors for alveolar
symptoms would not be characteristic of either injury. The detection of protein, red cells, and
IgA nephropathy or Henoch–Schönlein purpura. white cells on urinalysis could be consistent with
anti-GBM disease, although this disease is more
ANCA-Associated Vasculitis likely to be associated with rapidly progressive
Antineutrophil cytoplasmic antibody (ANCA)– glomerulonephritis with a fulminant course that
associated vasculitides include eosinophilic gran- results in rapid deterioration of kidney function.
ulomatosis with polyangiitis (EGPA), granuloma- However, in an observational study involving
tosis with polyangiitis (GPA), and microscopic patients with anti-GBM disease, milder renal in-
polyangiitis (MPA). Patients with EGPA, GPA, or volvement occurred in a higher percentage of pa-
MPA can have concurrent pulmonary and renal tients than expected.3 Anti-GBM disease remains
involvement. a possible diagnosis, but the normal creatinine
EGPA typically progresses through three stages. level decreases the likelihood of this condition.
The first stage involves refractory atopic symp-
toms, which are accompanied by peripheral Systemic Lupus Erythematosus
eosinophilia in the second stage, and the final Systemic lupus erythematosus (SLE) is a chronic
stage involves a systemic vasculitis that is her- autoimmune disease of unknown cause. In this
alded by constitutional symptoms.1 This patient patient, the presence of microscopic hematuria
did not have symptoms or signs of concurrent, and proteinuria in the context of multisystemic
persistent, or refractory asthma. There were no symptoms warrants consideration of SLE. His
nasal or sinus symptoms or findings suggestive evolving respiratory symptoms would be consis-
of peripheral neuropathy, which are often ob- tent with SLE, which commonly results in pul-

monary disease. His early chest pain and pleural in the absence of other clinical criteria.5 In this
effusion could be manifestations of pleuritis and patient, renal biopsy would not only provide di-
serositis, respectively. SLE is associated with an agnostic confirmation but also inform progno-
increased risk of infection, given the associated sis and guide therapy.
leukopenia and hypocomplementemia, which SLE is the diagnosis that is most likely to
could have conferred a predisposition to pneu- explain this patient’s symptoms and findings. I
monia in this patient. Finally, the extensive pul- suspect that the diagnostic test in this case was
monary emboli found on admission in this pa- renal biopsy with immunofluorescence staining.
tient would be consistent with the predilection
for thromboembolism among patients with SLE, Dr . Sh aun F. Fi t z ger a l d’s
especially those with concomitant antiphospho- Di agnosis
lipid antibodies.
Antiphospholipid syndrome can be a primary Systemic lupus erythematosus.
disorder or can occur in association with auto-
immune diseases, such as SLE. The hallmark Di agnos t ic Te s t ing
feature is a prothrombotic state that results in
both arterial and venous thromboembolism. The Dr. Weizhen Tan: Testing was negative for anti-
patient’s extensive pulmonary emboli invoke con- GBM antibodies and ANCAs. Testing was posi-
cern for such hypercoagulability. In addition, he tive for lupus anticoagulant, ANAs (titer, 1:320),
had a history of migraines and possible Raynaud’s and anti-dsDNA antibodies (titer, 1:640), with a
phenomenon, both of which are associated with low C3 level (74 mg per deciliter; reference
antiphospholipid syndrome. range, 81 to 157). Testing of a random urine
Other aspects of this patient’s presentation sample revealed 1.1 mg of protein per 1.0 mg of
could also be attributed to SLE. On evaluation at creatinine (reference value, <0.2), and granular
this hospital, he had symptoms suggestive of casts were observed on microscopic examination
psychosis, which could be neuropsychiatric man- of the urinary sediment. The most likely diagno-
ifestations of SLE, including SLE involving the sis was lupus nephritis. Because the proteinuria
central nervous system (known as CNS lupus). was not in the nephrotic range (i.e., the urinary
Fatigue and loss of appetite are also common protein level was <3.5 g per day)6 and the creati-
symptoms of SLE. The patient’s absolute lym- nine level was normal, a highly active class III or
phocyte count was less than 1500 cells per mi- IV lupus nephritis was unlikely. Percutaneous
croliter, a finding consistent with lymphopenia, renal biopsy was performed.
which is often observed with SLE. In patients
with SLE, anemia is often due to autoimmune Pathol o gic a l Discussion
hemolysis; this patient did not have an elevated
bilirubin level, but a direct antiglobulin test Dr. Cynthia K. Harris: The tissue from the core bi-
(direct Coombs’ test) would be helpful in ruling opsy of the kidney was divided for light micros-
out hemolysis. copy, immunofluorescence staining, and electron
American College of Rheumatology criteria microscopy. Light microscopy (Fig. 3A) revealed
and Systemic Lupus Erythematosus International mild mesangial hypercellularity and expansion
Collaborating Clinics (SLICC) criteria can aid in of mesangial matrix, as well as thickening of the
the diagnosis of SLE.4,5 In this patient, it would glomerular basement membrane without dupli-
be helpful to obtain levels of one or more of the cation. Masson’s trichrome staining revealed
following immunologic markers: antinuclear fuschinophilic subepithelial deposits along the
antibodies (ANAs), anti–double-stranded DNA glomerular basement membrane. Prominent pro-
(anti-dsDNA) antibodies, anti-Smith antibod- tein reabsorption droplets were seen within tu-
ies, a ntiphospholipid antibodies, or complement bular epithelial cells. Endocapillary proliferation,
in serum. The SLICC criteria require at least one glomerular necrosis, and crescent formation were
positive test for an immunologic marker. In the not seen.
presence of ANAs or anti-dsDNA antibodies, Direct immunofluorescence staining (Fig. 3B
results on renal biopsy that are compatible with through 3F), performed on a specimen of frozen
lupus nephritis would be diagnostic of SLE, even tissue, was positive for IgG, IgA, IgM, C3, and

C1q in the mesangium and along the glomerular membranous lupus nephritis was prednisone
basement membrane in a finely granular pattern. monotherapy. One study established that induc-
This finding is known as “full house” staining, tion therapy with prednisone plus cyclophospha-
owing to the staining for three immunoglobu- mide was more effective than prednisone alone.9
lins (IgG, IgA, and IgM) and two complement A lower-dose protocol of cyclophosphamide has
factors (C3 and C1q). Staining for kappa and since been adopted by many nephrologists.10,11
lambda immunoglobulin light chains was pos- Larger trials established that induction therapy
itive with a granular pattern and a similar in with prednisone plus mycophenolate mofetil was
tensity. effective in patients with lupus nephritis; similar
Scanning electron microscopy (Fig. 3G) re- results were observed in subgroups of patients
vealed segmental podocyte foot process efface- with membranous lupus nephritis.12,13 Trials have
ment. Abundant amorphous deposits were pres- thus established mycophenolate mofetil and cy-
ent in a diffuse subepithelial distribution. Some clophosphamide as acceptable induction agents
intervening “spikes” of glomerular basement for the treatment of membranous lupus nephri-
membrane occasionally bridged over the deposits. tis.14 Ultimately, 12 to 37% of patients with
The endothelial cells contained numerous tubu- membranous lupus nephritis and nephrotic pro-
loreticular inclusions. teinuria have progression to end-stage kidney
Given the diffuse thickening of the glomeru- disease, so treatment of patients with membra-
lar basement membrane and the subepithelial nous lupus nephritis who have clinically signifi-
deposits and intervening “spikes” of membrane, cant proteinuria or nephrotic syndrome is war-
the findings can best be classified as class V ranted.15
lupus nephritis, which is also known as mem- After membranous lupus nephritis was diag-
branous lupus nephritis.7 Although the Interna- nosed in this patient, induction therapy with
tional Society of Nephrology–Renal Pathology pulse doses of glucocorticoids and cyclophos-
Society classification system describes six class- phamide was initiated, given the severity of his
es of lupus nephritis, biopsy results are most symptoms and pulmonary involvement. Preser-
likely to be consistent with class II through V vation of fertility with sperm banking was pur-
disease. Class III or IV lupus nephritis confers sued before induction therapy with cyclophospha-
the worst prognosis; patients with class V dis- mide was begun. His treatment was transitioned
ease (membranous lupus nephritis) and simulta- to maintenance therapy with mycophenolate
neous proliferative class III or IV disease have mofetil, as well as adjuvant therapy with hydroxy-
worse outcomes than patients with membranous chloroquine and lisinopril.
lupus nephritis alone. To rule out lupus cerebritis, magnetic reso-
nance imaging of the head and magnetic reso-
nance angiography of the head and neck were
Pathol o gic a l Di agnosis
performed, and both studies were normal. In
Membranous lupus nephritis. addition, lumbar puncture was performed, and
cerebrospinal fluid (CSF) analysis was normal,
including the results of CSF electrophoresis and
Discussion of M a nagemen t
an autoimmune panel.
Dr. Tan: Lupus nephritis is a difficult disease to Given the possibility of antiphospholipid syn-
treat but is widely studied, and evidence-based drome, anticoagulation therapy for pulmonary
clinical practice guidelines are available.8 Given embolism was transitioned from enoxaparin to
that untreated, biopsy-confirmed, active class III warfarin during the hospitalization. However,
or IV lupus nephritis is associated with poor subsequent testing for antiphospholipid syn-
outcomes, most of the evidence for treatment is drome was negative. The patient has continued
based on data regarding active class III or IV to receive extended anticoagulation therapy for
disease. Membranous lupus nephritis accounts active SLE. A switch to the direct oral anticoagu-
for only 10% of all cases of lupus nephritis, so lant apixaban was considered, but the patient
data regarding membranous lupus nephritis are has opted to continue with warfarin because of
limited to a few studies.8 his preference for a medication with once-daily
The original standard induction therapy for dosing.

A B
100 µm
C D
100 µm 100 µm
E F
100 µm 100 µm

Figure 3 (facing page). Kidney-Biopsy Specimen. addition to standard induction therapy with glu-
Light microscopy with hematoxylin and eosin staining cocorticoids and cyclophosphamide or mycophe-
(Panel A) shows mesangial hypercellularity (arrowhead) nolate mofetil, had a greater response with re-
and thickening of the glomerular basement membrane spect to proteinuria and the estimated glomerular
without duplication (arrow). Immunofluorescence stain filtration rate than those who received placebo
ing for IgG, IgA, IgM, C3, and C1q (Panels B through F,
plus standard induction therapy, without an in-
respectively) is positive in the mesangium and along
the glomerular basement membrane. Electron micros crease in adverse events.16 Nine months after the
copy (Panel G) shows subepithelial deposits with inter patient had been admitted to this hospital, treat-
vening “spikes” of glomerular basement membrane ment with belimumab was started, and mainte-
(arrows). nance therapy with mycophenolate mofetil was
continued.
Twenty-one months after the initial diagno-
Seven months after admission to this hospi- sis, the patient is doing well, with stable kidney
tal, routine laboratory testing revealed an albu- function. With belimumab infusions and contin-
min level of 2.8 g per deciliter, an increase in ued mycophenolate mofetil therapy, his last uri-
proteinuria (from 1.1 mg of protein per 1.0 mg nary protein:creatinine ratio was normal (0.2 mg
of creatinine to 3.6 mg of protein per 1.0 mg of of protein per 1.0 mg of creatinine on a first
creatinine), a decrease in the C3 and C4 levels, morning void), and glucocorticoid therapy has
and an elevation in the titer of anti-dsDNA anti- been tapered.
bodies. A flare of membranous lupus nephritis
was diagnosed, and treatment with alternative Fina l Di agnosis
agents was considered.
Belimumab, an IgG monoclonal antibody that Systemic lupus erythematosus with membranous
inhibits B-cell survival and maturation, has been lupus nephritis.
studied in patients with lupus nephritis (includ-
This case was presented at Pediatric Grand Rounds.
ing 16% with membranous lupus nephritis). Disclosure forms provided by the authors are available with
Those who received belimumab, administered in the full text of this article at NEJM.org.
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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 9-2023: A 20-Year-Old Man

Pr e sen tat ion of C a se

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The New England Journal of Medicine

Table 1. Laboratory Data.*

Reference Range, On Admission, Reference Range, On Admission,

auscultation, but the left lung had diminished Differ en t i a l Di agnosis

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Figure 2. Imaging Studies Obtained on Current Presentation.

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The New England Journal of Medicine

Poststreptococcal Glomerulonephritis served in patients with EGPA. In addition, there

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The New England Journal of Medicine

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The New England Journal of Medicine

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