T h e NE W ENGL A ND JOUR NA L o f MEDICINE

CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL

Founded by Richard C. Cabot
Nancy Lee Harris, M.D., Editor Eric S. Rosenberg, M.D., Associate Editor
Jo-Anne O. Shepard, M.D., Associate Editor Alice M. Cort, M.D., Associate Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor





Case 28-2011: A 74-Year-Old Man with
Pemphigus Vulgaris and Lung Nodules

Eleftherios Mylonakis, M.D., Victorine V. Muse, M.D.,
and Mari Mino-Kenudson, M.D.

PRESENTATION OF CASE

Dr. Omobolaji T. Campbell (Infectious Diseases): A 74-year-old man was seen in
the surgery clinic at this hospital for evaluation of lung nodules.
A diagnosis of pemphigus vulgaris had been made 5 months earlier after a 2-
month history of skin lesions that had progressed from erosions on the patients lips
to multiple bullae and crusted erosions on his face, trunk, scalp, lips, and oral
mucosa. The erosions and bullae were itchy and painful and associated with diffi-
culty swallowing, anorexia, and weight loss of 1.4 kg. The patient had a history of
diabetes mellitus, hypertension, and hyperlipidemia. Medications included
enalapril, nifedipine, loratadine, simvastatin, hydrochlorothiazide, metformin, and
acetylsali-cylic acid; all these except metformin had been discontinued by the
patients pri-mary care physician when the rash first developed, before evaluation
by the derma-tologist. On examination by the dermatologist at that time, there were
multiple pink crusted plaques and flaccid blisters on the trunk, face, and scalp and
erosions on the oral mucosa. Nikolskys sign (blistering of the skin and mucosa as a
response to slight rubbing or pressure) was positive on the left upper back. The
serum level of IgG antibodies to desmoglein 1 was 180.7 U (reference range,
<14.0), and to des-moglein 3 was 154.6 U (reference range, <9.0). Pathological
examination of a skin-biopsy specimen of the lesions on the lower back showed
intraepidermal blistering that was consistent with pemphigus vulgaris.
The administration of prednisone (60 mg daily) was begun; the lesions rapidly
improved, and the dose was reduced to 40 mg daily. Hyperglycemia developed, and
treatment with glipizide was begun. Two weeks later, the serum sodium level was
131 mmol per liter (reference range, 135 to 145), the chloride level 97 mmol per
liter (reference range, 100 to 108), and the glucose level 213 mg per deciliter (11.8
mmol per liter) (reference range, 70 to 110 mg per deciliter [3.9 to 6.1 mmol per
liter]); serum levels of potassium, carbon dioxide, calcium, total protein, albumin,
and globulin were normal, as were the results of tests for liver and renal function
and thiopurine methyltransferase activity. Urinalysis showed glucose 2+ (300 to
500 mg per deciliter [16.7 to 27.8 mmol per liter]); results were otherwise normal.
Three weeks later, a skin test for tuberculosis was negative. The dose of prednisone
was gradually increased to 60 mg daily, and treatment with azathioprine (initial
dose, 50 mg daily) was begun as a glucocorticoid-sparing agent.







From the Division of Infectious Dis-eases
(E.M.) and the Departments of Radiology
(V.V.M.) and Pathology (M.M.-K.),
Massachusetts General Hos-pital; and
the Departments of Medicine (E.M.),
Radiology (V.V.M.), and Patholo-gy
(M.M.-K.), Harvard Medical School
both in Boston.

N Engl J Med 2011;365:1043-50.
Copyright 2011 Massachusetts Medical Society.

N ENGL J MED 365;11 NEJM.ORG SEPTEMBER 15, 2011 1043

The New England Journal of Medicine
Downloaded from nejm.org on September 30, 2013. For personal use only. No other uses without
permission. Copyright 2011 Massachusetts Medical Society. All rights reserved.
T h e NE W ENGL A ND JOUR NA L o f MEDICINE

At follow-up in the dermatology clinic 1 month
later, the patient reported hoarseness and a cough
with yellow sputum of 1 weeks duration. Despite
resolution of many of the skin lesions, the oral
lesions persisted. He reported eating and drinking
well; however, his weight had decreased from 60.0
kg to 56.4 kg. The administration of trimeth-
oprimsulfamethoxazole for prophylaxis against
infection was begun, and the patient was referred to
an otolaryngologist; fiberoptic laryngoscopic
examination reportedly revealed involvement of the
vocal cords with pemphigus. Testing for paraneo-
plastic pemphigus IgG autoantibodies was nega-
tive. The dose of azathioprine was increased to 100
mg daily.
At follow-up 5 months after the onset of symp-
toms, the patient reported less discomfort of his
oral mucosa and resolution of his hoarseness, but
he reported new painful lesions on his back and
burning with urination, without urinary frequency,
hematuria, or blood in his stool. Physical exami-
nation revealed new crusted erosions on his back.
The white-cell count was 11,900 per cubic milli-
meter (88% neutrophils). Urinalysis revealed a
glucose level greater than 1000 mg per deciliter
(55.5 mmol per liter), trace amounts of blood, and 3
to 4 red cells, 10 to 15 bacteria, and 3 to 10 epi-
thelial cells per high-power field. A urine culture
was sterile. Ultrasonography of the kidneys per-
formed at another hospital reportedly revealed bi-
lateral, nonobstructing renal calculi. A computed
tomographic (CT) scan of the abdomen and pel-vis
reportedly showed nephrolithiasis and pros-tatic
hypertrophy, without obstruction, with inci-dental
findings of a pulmonary consolidation and lung
nodules in the right lower lobe. Treatment with
insulin was begun for persistent hypergly-cemia.

Five weeks before this evaluation, the dose of
azathioprine was increased to the goal dose of 150
mg daily. The patient reported soreness of his
tongue; examination revealed white plaques on the
lateral edges of the tongue. Fluconazole (100 mg
orally, once weekly) was initiated for presumed
thrush. CT of the chest reportedly revealed en-
largement of parenchymal and pleural densities
(predominantly in the right lower lung) and nod-
ules in both lower lobes, which had not been pres-
ent 4 years earlier.
18
F-fluorodeoxyglucoseposi-
tron-emission tomography (FDG-PET) reportedly
revealed FDG avidity of the nodules in both lower
lobes and of the pleura of the right lung. Seventeen
days before this evaluation, the white-

cell count was 5200 per cubic millimeter (90%
neutrophils); the dose of azathioprine was de-
creased to 50 mg daily. The patient was referred
to the surgery clinic at this hospital for evalua-
tion of the lung nodules.
The patient reported a weight loss of 11.3 kg
associated with his illness; he had regained 4.5 kg
after the symptoms had improved. He had per-
sistent fatigue and dysuria; he did not have back
pain, difficulty swallowing, cough, sore throat,
hoarseness, blood in the urine or stool, headache,
fever, chills, or sweats. He had had an episode of
chest pain with normal cardiac perfusion 6 months
earlier, mild-to-moderate left ventricular hypertro-
phy according to echocardiography, and prostatic
hypertrophy; he had also undergone an appen-
dectomy. Oral medications included prednisone,
azathioprine, metformin, glipizide, acetylsalicylic
acid, acetaminophen, ergocalciferol, calcium car-
bonate, and trimethoprimsulfamethoxazole, with
tramadol as needed for pain. Topical medications
included mupirocin ointment, gentian violet, and
halobetasol propionate ointment for active skin
lesions, and viscous lidocaine as needed for pain-
ful mouth sores. The patient was allergic to rosi-
glitazone maleate, which had caused a rash. He was
from Brazil and had immigrated to the United
States more than 10 years earlier. He lived in New
England with his wife and was retired. He had
stopped smoking 40 years earlier, after 5 pack-
years, and did not drink alcohol or use illicit drugs.
He was monogamous with his wife and had trav-
eled only to Florida; he had not returned to South
America. There was no history of exposure to
blood products or animals. His father had died of
stomach cancer at 69 years of age, and his moth-er
had died during childbirth. One of his eight
children had died of an immune problem; there
was no family history of skin diseases.
On examination, the height was 157.5 cm and
the weight 54.9 kg. The vital signs were normal.
There were multiple healed pink scars on the chest,
abdomen, inguinal folds, and scalp; several active
ulcers on the back in various stages of heal-ing; and
several broad erosions on the hard and soft palate.
The remainder of the examination was normal.
Pulmonary-function tests revealed a forced vital
capacity of 2.42 liters (76% of the predicted value)
and a forced expiratory volume in 1 second of 1.83
liters (73% of the predicted value), and the carbon
monoxide diffusing capac-ity was 80% of the
predicted value. The white-cell count was 9800 per
cubic millimeter, and the

1044 N ENGL J MED 365;11 NEJM.ORG SEPTEMBER 15, 2011

The New England Journal of Medicine
Downloaded from nejm.org on September 30, 2013. For personal use only. No other uses without
permission. Copyright 2011 Massachusetts Medical Society. All rights reserved.
CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL


serum electrolyte levels were 134 mmol of sodium per liter, 5.4 mmol
of potassium per liter (refer-ence range, 3.4 to 4.8), and 95 mmol of
chloride per liter. The remainder of the complete blood count was
normal, as were tests of coagulation and liver and kidney function.
A diagnostic procedure was performed.




A












B












C











Figure 1. Imaging Studies.
CT of the chest without the administration of contrast material shows multiple bilateral ill-defined pulmonary nodules (Panel
A). When CT is combined with posi-tron-emission tomographic (PET) imaging, the nod-ules have marked FDG avidity,
indicating increased metabolic activity (Panel B). A combination PET-CT scan also shows increased metabolic activity in the
right posterior pleura that is not seen in the CT scan alone (Panel C).