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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 1-2012: An 82-Year-Old Man

with Persistent Ulcers on the Hands
Daniela Kroshinsky, M.D., Mai P. Hoang, M.D., and Robert P. Hasserjian, M.D.

Pr e sen tat ion of C a se

From the Departments of Dermatology
(D.K.) and Pathology (M.P.H., R.P.H.), Massachusetts General Hospital; and the Departments of Dermatology (D.K.) and Pathology (M.P.H., R.P.H.), Harvard Medical
School both in Boston.
N Engl J Med 2012;366:166-74.
Copyright 2012 Massachusetts Medical Society.

166

Dr. Sarah Gee (Dermatology): An 82-year-old man was admitted to this hospital because
of persistent skin lesions on the hands.
The patient had a history of diabetes mellitus and recurrent hidradenitis suppurativa. Five weeks before admission, he was admitted to another hospital because
of drainage from a perineal abscess that was unresponsive to cephalexin. On examination, he reportedly had a small abrasion on his left hand, which he thought
was caused by a dog bite. The administration of cephalexin was discontinued, and
piperacillintazobactam and vancomycin were begun. During the following week,
increasing erythema and an enlarging hemorrhagic bulla developed on the dorsum
of the left hand and a diffuse, urticarial, and purpuric rash developed on the torso.
Laboratory testing reportedly revealed thrombocytopenia. Dbridement of the lesion of the left hand was performed; pathological examination of a specimen reportedly showed acute inflammation and granulation tissue. After dbridement,
the lesion worsened and similar lesions developed on the right hand, on the metacarpophalangeal joints. The lesions were reportedly painful to the touch and to
manipulation, with ulceration extending to the tendons. Glucocorticoids were administered. On the 10th hospital day, a biopsy specimen of the skin of the right
abdomen was obtained; pathological examination reportedly showed leukocytoclastic vasculitis and no microorganisms. The administration of piperacillintazobactam
and vancomycin was stopped, as was subcutaneous heparin (begun during admission),
and ciprofloxacin and linezolid were begun, in conjunction with a topical antimicrobial solution for the hands. The lesions expanded to include the proximal interphalangeal joints and became more erosive and painful. On the 13th day, the patient was
transferred to a second hospital for evaluation and management of the skin lesions.
At the second hospital, the patient reported weight loss of approximately 2.3 kg
per week during the previous month and intermittent diarrhea. On examination, the
temperature was normal. On the dorsal surfaces of the hands were well-demarcated,
edematous, friable, erythematous-to-violaceous plaques, with gray discoloration at
the margins (Fig. 1A). Smaller violaceous, erythematous, edematous plaques were
present on the trunk and thighs. A biopsy specimen of the skin on the dorsum of the
right hand was obtained; pathological examination revealed a superficial and deep,

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dense, diffuse neutrophilic infiltrate. Staining for

microorganisms was negative, and cultures were
sterile. The serum level of sodium was 130 mmol
per liter (reference range, 135 to 145), and levels
of the other electrolytes were normal. Tests of
liver function were normal, and testing for antibodies to the platelet factor 4heparin complex
was negative; other test results are shown in
Table 1. The administration of antibiotics was
stopped, higher-dose systemic glucocorticoids were
begun, and local wound care was performed, with
partial improvement.
The patient was discharged home on the fifth
day, taking prednisone (70 mg orally daily) with
instructions to initiate a taper in 2 to 3 weeks.
He also was prescribed an intensive wound-care
regimen, with the assistance of a home nurse.
Shortly after discharge, the prednisone dose was
tapered from 70 mg daily to 40 mg daily, the
administration of cyclosporine (300 mg daily) was
begun, and intralesional triamcinolone acetonide
(to a total of 60 mg daily) was injected.
Six days before admission to this hospital, a
biopsy specimen of the skin on the dorsum of
the right hand was obtained; pathological examination reportedly revealed neutrophilic dermatitis, with a suggestion of follicular perforation and folliculitis; no microorganisms were
seen. The next day, levels of serum electrolytes,
total bilirubin, total protein, globulin, and calcium were normal, as were tests of liver function; other laboratory-test results are shown in
Table 1. Three days later, the lesions seemed improved; the cyclosporine dose was decreased to
100 mg orally daily, dapsone (100 mg daily) was
started, and prednisone was maintained at 40 mg
daily. During the next 2 days, the lesions on the
patients hands worsened. He was referred to this
hospital and admitted because of increased pain
and oozing of the lesions.
The patient reported feeling well except for
his hands. He had a history of hidradenitis suppurativa, with recurrent abscesses, for more than
20 years, for which multiple antibiotics had been
administered; diabetes mellitus, for which he had
recently started taking insulin; hypertension;
hyperlipidemia; cholelithiasis; a malignant melanoma of the back, which had been excised;
macrocytic anemia with low folate levels; multinodular goiter; diverticulosis; microhematuria;
chronic obstructive pulmonary disease; bradycardia, for which a cardiac pacemaker had been
n engl j med 366;2

Figure 1. Clinical Photographs of the Patient.

At the time of the patients admission to the second
hospital, there are partially denuded bullous lesions on
the dorsal surface of both hands, extending over the
fingers (Panel A, photograph courtesy of Drs. Kristina
Collins and Harley Haynes, Department of Dermatology,
Brigham and Womens Hospital). On admission to this
hospital, an erythematous, bullous lesion is seen on the
right arm (Panel B, photograph courtesy of Dr. Ines Wu,
Department of Dermatology, Massachusetts General
Hospital). After treatment with infliximab, the lesion
on the right arm is nearly healed (Panel C, photograph
courtesy of Dr. Sarah Gee, Department of Dermatology,
Massachusetts General Hospital).

inserted; and bilateral leg edema. He had had

herniorrhaphies and an appendectomy. Other medications included lisinopril and aspirin. He was
allergic to penicillin. He was retired, lived with
his wife, smoked cigarettes, and drank alcohol
in moderation. He had no history of exposures

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Table 1. Laboratory Data.*

Reference Range,
Adults

26 Days before
Admission,
2nd Hospital

5 Days before
Admission

On Admission,
This Hospital

2nd Day

4th Day

Hematocrit (%)

41.053.0

34.3

33.0

28.2

26.4

23.5

Hemoglobin (g/dl)

13.517.5

11.8

11.2

9.8

9.0

8.2

450011,000

9100

8900

9600

7100

9900

Neutrophils

4070

96

84

85

77

79

Band forms

010

12

Variable

White-cell count (per mm

3)

Differential count (%)

Lymphocytes

2244

12

13

Monocytes

411

Eosinophils

08

Metamyelocytes

Myelocytes

Reactive lymphocytes
Platelet count (per mm3)
Mean corpuscular volume (m3)
Urea nitrogen (mg/dl)
Creatinine (mg/dl)

150,000400,000

160,000

81,000

81,000

81,000

70,000

80100

101.0 (ref 8095)

107

106

106

106

825

33

28

33

30

39

1.0

0.601.50

0.87

1.07

1.00

1.04

Normal, 60

>60

>60

>60

>60

70110

135

163

138

116

Total

0.01.0

1.1 (ref 0.21.2)

Direct

0.00.4

Estimated glomerular filtration

rate (ml/min/1.73 m2)
Glucose (mg/dl)
Bilirubin (mg/dl)

Albumin (g/dl)

3.35.0

1.0

1.3
0.6

2.8

3.0

3.0

* Ref denotes reference range at the second hospital. 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 glucose to millimoles per liter, multiply by
0.05551. To convert the values for bilirubin to micromoles per liter, multiply by 17.1.
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 conditions that could affect the results.
Theymay therefore not be appropriate for all patients.

to chemicals. There was no family history of

similar skin lesions, autoimmune disorders, or
inflammatory bowel disease.
On examination, the respiratory rate was
30breaths per minute and the oxygen saturation
was 97% while the patient was breathing ambient air; other vital signs were normal. There were
violaceous, edematous, denuded plaques on the
metacarpophalangeal joints of both hands and
on both elbows (Fig. 1B), as well as bilateral leg
edema. The serum iron level was 50 g per deciliter (9 mol per liter; reference range, 45 to 160 g
per deciliter [8 to 29 mol per liter]), iron-binding
capacity 220 g per deciliter (39 mol per liter;
168

reference range, 228 to 429 g per deciliter [41

to 77 mol per liter]), and ferritin level 540 ng per
milliliter (reference range, 30 to 300, in men). The
serum levels of electrolytes, calcium, magnesium,
phosphorus, total protein and globulin, free thyroxine, lactate dehydrogenase, vitamin B12, folate,
and glucose-6-phosphate dehydrogenase were normal, as were tests of liver function. Testing was
negative for rheumatoid factor; evidence of hepatitis A, B, and C viruses; antiphospholipid antibodies; and lupus anticoagulant. Other test results are shown in Table 1. The administration
of trimethoprimsulfamethoxazole was begun.
No Bence Jones proteins were detected in a con-

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centrated urine specimen. Urinalysis revealed

cloudy yellow urine, trace protein, 3+ occult blood,
20 to 50 red cells per high-power field, and 3 to
5 hyaline casts per low-power field.
On the fourth day, a diagnostic procedure
was performed.

Differ en t i a l Di agnosis
Dr. Daniela Kroshinsky: I am aware of the diagnosis
in this case. This patient presented with a violaceous bullous lesion on the hand after a possible
dog bite. The lesion expanded on dbridement,
and new lesions arose on the other hand. The
cutaneous findings were accompanied by diarrhea and weight loss, but the patient was otherwise asymptomatic. The process was initially
thought to be consistent with a necrotizing hemorrhagic cellulitis.
The differential diagnosis that I would consider for these ulcerative, bullous, necrotic hand
lesions includes infection (bacterial, mycobacterial, protozoal, fungal, or viral); a vasculitis (e.g.,
vasculitis associated with antineutrophil cytoplasmic antibodies [ANCA] or vasculitis of mediumsize vessels); and neutrophilic dermatoses (e.g.,
pyoderma gangrenosum or Sweets syndrome).
Other blistering processes that often affect the
hands but are not clinically consistent with this
patients presentation are porphyria cutanea
tarda and epidermolysis bullosa acquisita.
Infection

An infectious cause of the initial ulceration should

be considered in view of the history of a dog bite,
which can transmit several types of infectious organisms. The differential diagnosis would include bacterial infections (e.g., necrotizing cellulitis), mycobacterial infections (e.g., Mycobacterium
ulcerans), protozoal infections (e.g., leishmaniasis), deep fungal infections (e.g., sporotrichosis),
and viral infections (e.g., orf). Most of these causative agents are not endemic in the northeastern
United States, and this patient reported no recent
or remote travel to areas where they are endemic.
The main bacterial infections to consider in
association with dog bites are from staphylococci, streptococci, anaerobes, and pasteurella
species. The aggressive nature of this patients
initial lesion also requires consideration of more
aggressive organisms, such as clostridium. Many
cases of necrotizing cellulitis result from local

trauma and are more often seen in patients with

a history of diabetes, which this patient has.
Despite the pathological diagnosis of necrotizing cellulitis, there was no crepitus on examination of the patient or gas on imaging, although
this finding is not seen in all forms of necrotizing cellulitis. He had no other signs of infection
(e.g., fever or leukocytosis), he had no response to
broad-spectrum antibiotics, cultures of the lesion
were sterile, and his lesions worsened with dbridement; in addition, lesions developed in nontraumatized areas in the absence of signs of systematized infection. For these reasons, infection
seemed unlikely.
Vasculitis

Certain forms of vasculitis can cause deep, painful ulceration, particularly vasculitis of mediumsize vessels and the ANCA-associated forms of
vasculitis. These were less likely diagnoses in
this patient because of the previous biopsy specimen that lacked evidence of vasculitis, the absence of respiratory symptoms that would suggest necrotizing granulomatous inflammation of
the upper and lower respiratory tracts, and the
glomerulonephritis that would be present in Wegeners granulomatosis. The peak age at onset of
this condition is 45 to 65 years, younger than this
patient. Cutaneous polyarteritis nodosa is a condition of necrotizing vasculitis of medium-size
vessels that is limited to the skin. It would be
unlikely in this patient, since a manifestation is
painful nodules that subsequently ulcerate, predominantly on the legs. Additional findings in
cases of cutaneous polyarteritis nodosa include
fever, myalgias, arthralgias, peripheral neuropathy, livedo reticularis, and atrophie blanche, all
of which were absent in this patient. Repeat biopsy with close attention to any blood-vessel abnormalities and levels of cytoplasmic ANCA and
perinuclear ANCA would help to rule out these
forms of vasculitis.
Neutrophilic dermatoses

Pathergy

The patients original lesion appeared to arise after minor skin trauma, and during the hospital
stay, he had evidence of new skin lesions arising
at sites of iatrogenic skin trauma. This phenomenon, known as pathergy, is an inflammatory
response that develops after intradermal trauma
and is manifested as erythematous-to-violaceous

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papules, plaques, and pustules, sometimes with

secondary ulceration. A diagnostic test for pathergy
is often used to confirm a suspicion of Behets
disease an 18-gauge needle is inserted at an
angle through the dermis, and the appearance of
lesions within 48 hours after insertion is indicative of a positive test. Pathergy occurs not only in
Behets disease but also in acute febrile neutrophilic dermatosis (Sweets syndrome), pyoderma gangrenosum, bowel-associated dermatosisarthritis
syndrome, and rheumatoid arthritis. I most often
see pathergy associated with these conditions as
an incidental finding on physical examination,
manifesting as lesions arising at sites of intravenous catheter placement, venous sticks, skin biopsies, and other routine procedures that result
in piercing of the dermis, as in this patient. The
finding of pathergy should halt any further dbridement or surgery, since these procedures would
extend the process and would most likely result
in an ongoing cycle of expansion and further
dbridement that could have catastrophic consequences.
Pyoderma Gangrenosum

Pyoderma gangrenosum is a neutrophilic dermatosis that presents as a rapidly advancing painful

ulcer, most often on the legs, with an irregular,
violaceous or gunmetal gray, undermined border.1
An atypical form appears on the hands, arms, or
face, with deep erosions or superficial ulcerations
that have a violaceous or blue-gray, bullous or
granulomatous-appearing border. This form has
also been referred to as neutrophilic dermatoses
of the hands, and the patients clinical presentation is consistent with this variant.
Up to 70% of cases of pyoderma gangrenosum
are associated with an underlying condition, such
as inflammatory bowel disease, rheumatoid arthritis, and hematologic diseases (e.g., acute myeloid
leukemia or myelodysplastic syndromes, hairycell leukemia, or monoclonal gammopathy).1 This
patient reported a recent history of diarrhea and
weight loss, which raises the possibility of an
underlying inflammatory bowel disease, although
presentation at his age would be unusual. Chronic,
atypical cases of pyoderma gangrenosum, like the
one in this patient, are often associated with acute
myeloid leukemia, myelodysplastic syndromes, and
IgA monoclonal gammopathies.1 This patient has
thrombocytopenia and anemia, raising concern
for a primary bone marrow disorder. Another
noteworthy clinical finding in this patient is his
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prompt response, at least initially, to systemic glucocorticoids.

Criteria for the diagnosis of pyoderma gangrenosum have been proposed.1,2 Major criteria
are rapid progression of a painful, necrolytic, cutaneous ulcer that has an irregular, violaceous,
and undermined border and the ruling out of
other causes of cutaneous ulceration. Minor criteria are a history that is suggestive of pathergy,
the presence of a systemic disease associated with
pyoderma gangrenosum, the histopathological
finding of dermal neutrophilia, and a rapid response to systemic glucocorticoid treatment. This
patient meets both major criteria and three of
the four minor criteria for this diagnosis.
Sweets Syndrome

The diagnosis of acute febrile neutrophilic dermatosis (Sweets syndrome) requires two major
criteria (the abrupt occurrence of edematous erythematous-to-violaceous cutaneous lesions and a
biopsy specimen that shows superficial edema
and a deep, dense neutrophilic infiltrate without
vasculitis) and at least two minor criteria (an associated underlying condition or exposure, fever,
leukocytosis, and a rapid response to systemic
glucocorticoid use). Like pyoderma gangrenosum,
Sweets syndrome is characterized by pathergy,
as seen in this case. Also, 15% of adult cases of
Sweets syndrome are associated with hematologic neoplasms. The syndrome is also seen in
patients who have solid-organ cancers, upper respiratory or gastrointestinal infections, human
immunodeficiency virus infection, or inflammatory bowel disease; who have received vaccinations or other drugs (e.g., granulocyte colonystimulating factor and all-trans retinoic acid); who
have undergone bowel-bypass surgery; or who
are pregnant. Sweets syndrome typically does not
induce the deep, progressive ulceration that was
seen in this patient; however, localized Sweets
syndrome of the hands and atypical pyoderma
gangrenosum (neutrophilic dermatoses of the
hands) are sometimes considered to be the same
entity.3 The patient did not have fever or leukocytosis, although he did have a response to glucocorticoids.
Summary

In this patient who had violaceous, bullous, and

necrotic ulcers of the hands and arms; pathergy;
a biopsy specimen that revealed a dense neutrophilic infiltrate; and an absence of systemic symp-

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toms, my diagnosis is atypical chronic pyoderma gangrenosum, probably in association with

a hematologic neoplasm. I would proceed with a
re-review of his biopsy specimens by the dermatopathology service and, if inconclusive, with a
repeat biopsy. I would recommend further evaluation for disorders associated with pyoderma
gangrenosum, including consultations from the
hematology and gastroenterology services.

Dr . Da niel a K roshinsk y s
Di agnosis
Atypical chronic pyoderma gangrenosum in association with a hematologic neoplasm.

Pathol o gic a l Discussion

Dr. Mai P. Hoang: Histologic sections of the skin
biopsy specimen taken at the first hospital revealed a dense infiltrate of neutrophils in the
dermis. The overlying epidermis shows acanthosis, and there is papillary dermal edema (Fig. 2A
and 2B). Microbiologic cultures and special staining for microorganisms were negative. These findings are consistent with a diagnosis of pyoderma
gangrenosum.
The following four distinctive clinical and
histologic variants of pyoderma gangrenosum
have been described: ulcerative, pustular, bullous, and vegetative.4 Lesions characterized by
ulceration are often associated with a systemic
disease, including arthritis, inflammatory bowel
disease, and monoclonal gammopathy. Pustular
lesions are characterized by subcorneal pustules,
papillary dermal edema, a dense neutrophilic
infiltrate, and an association with inflammatory
bowel disease. The bullous lesions have subepidermal vesiculation and a dense dermal neutrophilic infiltrate and are associated with hematologic neoplasms. The vegetative lesions (or
superficial granulomatous pyoderma) are characterized by pseudoepitheliomatous hyperplasia, dermal abscess, and palisading granulomatous reaction and are typically not associated with
systemic disease.4 This case would fit best with
the bullous variant, and thus a hematologic neoplasm should be suspected.
Dr. Robert P. Hasserjian: Bone marrow biopsy
and aspiration were performed on the fourth
hospital day. The biopsy specimen was normocellular for the patients age and showed maturing myeloid and erythroid elements. Many megan engl j med 366;2

Figure 2. Skin-Biopsy Specimen (Hematoxylin and Eosin).

Panel A shows epidermal hyperplasia with superficial
dermal edema and hemorrhage and a dense infiltrate
of neutrophils in the dermis resembling an abscess.
Panel B shows a dense dermal infiltrate of neutrophils
at a higher magnification.

karyocytes appeared dysplastic and small and

had hypolobated nuclei and simplified nuclear
contours (Fig. 3A). The aspirate smear revealed
frequent dysplastic myeloid cells, including
many forms with hypogranulated cytoplasm
and bilobed nuclei (pseudo-PelgerHut cells).
Erythroid maturation was normal, and the percentage of myeloblasts (3%) was not increased.
An iron stain of the bone marrow aspirate
showed the presence of abundant storage iron
and no ring sideroblasts. The peripheral-blood
smear showed circulating immature myeloid
elements (myelocytes and metamyelocytes) and
pseudo-PelgerHut cells (Fig. 3B); circulating
blasts were not seen. These morphologic findings were thought to be highly suspicious for a
myelodysplastic syndrome; this diagnosis was
confirmed by bone marrow cytogenetic analysis,
which revealed an abnormal, complex karyotype, including deletion of the long arm of chromosome 5 (Fig. 3C).

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13

14

19

14d

20

15

21

10

16

22

11

12

17

18

Figure 3. Biopsy Specimen of the Bone Marrow and Peripheral-Blood Smear.

The bone marrowbiopsy specimen (Panel A, hematoxylin and eosin) showed frequent small, dysplastic megakaryocytes with single or separated and rounded nuclear lobes (arrows). Myeloid dysplasia was manifested in the peripheralblood smear (Panel B) as pseudo-PelgerHut cells with bilobed nuclei and hypogranulated cytoplasm; a normal
neutrophil from another patient is shown in the inset for comparison. Cytogenetic analysis of the bone marrow
(Panel C, courtesy of the Center for Advanced Molecular Diagnostics, Brigham and Womens Hospital) revealed
an abnormal, complex karyotype. Arrows indicate a translocation between chromosomes 2 and 6, monosomies
of chromosomes 3, 12, and 18, deletion of the long arm of chromosome 5, and additional material on the long arm of
chromosome 17; also present were a ring chromosome (14d) and a marker chromosome (A) (bottom left).

On the basis of the presence of two morpho- marrow (<5%), and the percentage of blasts in
logically dysplastic lineages (myeloid and mega- the blood (<1%), this myelodysplastic syndrome
karyocytic), the percentage of blasts in the bone was classified as refractory cytopenia with mul172

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case records of the massachusetts gener al hospital

tilineage dysplasia, according to the 2008 World

Health Organization classification.5 The presence
of a complex karyotype is an adverse prognostic
feature. The International Prognostic Scoring System (IPSS) for patients with myelodysplastic syndrome incorporates the percentage of blasts in
the bone marrow, the number and degree of
cytopenias, and the cytogenetic findings into a
risk-group designation (low-risk, intermediate-1
risk, intermediate-2 risk, or high-risk). This patients disease would fall in the intermediate-2
group; patients in this group have a median survival of approximately 1 year.6
Dr. Hoang: A variety of cutaneous manifestations have been reported in association with
malignant tumors, including pyoderma gangre
nosum, Sweets syndrome, dermatomyositis, and
necrobiotic xanthogranuloma. The two neutrophilic dermatoses pyoderma gangrenosum
and Sweets syndrome are seen most often in
association with myeloid neoplasms, including
myelodysplastic syndromes (as in this case), myeloproliferative neoplasms, and acute leukemias.
Dermatomyositis, characterized by necrotic kera
tinocytes at the dermalepidermal junction and
marked dermal mucin deposition, is associated
with lymphomas and ovarian carcinomas. Necrobiotic xanthogranuloma, characterized by granulomatous inflammation, cholesterol clefts, and
striking multinucleated giant cells, is associated
with paraproteinemia.

Discussion of M a nagemen t

fective before the attempt to taper them, we initially continued prednisone at 40 mg per day and
increased the cyclosporine to 300 mg per day.
Because the lesions showed no response, we
added mycophenolate mofetil and tacrolimus
topical gel. The lesions continued to progress,
and new lesions appeared on the face and upper
arms. On the eighth day, the patient began
treatment with infliximab (a chimeric monoclonal antibody against TNF- that blocks TNF-
action and induces apoptosis of T cells that express TNF-), which has a rapid onset of action
and has been reported to be helpful in cases of
atypical pyoderma gangrenosum occurring on the
hands and arms.7-9 Infliximab is preferred over
other TNF- blockers because of its rapid onset
of action. The patient had a dramatic response,
with improvement in all his lesions (Fig. 1C).
However, his overall clinical status deteriorated,
with renal failure, volume overload, and pulmonary edema. Because the underlying hematologic
disorder conferred a poor prognosis, the patient
and his wife elected not to pursue aggressive
treatment; in consultation with the palliative care
service, care was transitioned to comfort measures only, and the patient died on the 29th hospital day.
Dr. Eric S. Rosenberg (Pathology): Are there any
questions or comments?
A Physician: I have heard team mentioned
during this conference. Would you describe how
the team functions?
Dr. Kroshinsky: At our hospital, the dermatology consult team consists of a full-time dermatologist who is assigned to the consult service
with a resident. On behalf of this patient, the
dermatology consult team dealt extensively with
the team of caregivers, including the primary
physicians and nurses and the consultants who
helped interpret the test results that led to the
diagnosis and the care plan.

Dr. Kroshinsky: The diagnosis of atypical pyoderma gangrenosum had been made at the second
hospital, and prednisone and cyclosporine had
been prescribed, with a clinical response. Treatment of pyoderma gangrenosum involves wound
care, including avoidance of trauma and dbridement; treatment of any underlying condition; and
immunosuppressive therapy.1 Although treatment
of inflammatory bowel disease may induce reA nat omic a l Di agnosis
mission of skin lesions in some patients, systemic
immunosuppression is often required. The avail- Pyoderma gangrenosum due to a myelodysplastic
able agents, including glucocorticoids, dapsone, syndrome (refractory cytopenia with multilineage
sulfapyridine, azathioprine, methotrexate, cyclo- dysplasia).
phosphamide, cyclosporine, mycophenolate mofe
This case was presented at the postgraduate course Dermatotil, tacrolimus, and tumor necrosis factor pathology Update, sponsored by the Harvard Medical School
(TNF-) inhibitors, vary in their speed of onset of Department of Continuing Education and Department of Patholaction, their side-effect profile, and their cost.1 ogy, Massachusetts General Hospital, Beth Israel Deaconess
Medical Center, and Brigham and Womens Hospital.
In consultation with the clinical team, and beDisclosure forms provided by the authors are available with
cause prednisone and cyclosporine had been ef- the full text of this article at NEJM.org.
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References
1. Callen JP, Jackson JM. Pyoderma gan-

grenosum: an update. Rheum Dis Clin

North Am 2007;33:787-802.
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FC, Perry HO. Pyoderma gangrenosum:
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