Acne Urticata Associated With Chronic Myelogenous Leukemia

JAN BRYDON, MD,' PAUL A. LUCKY, MD,* AND THOMAS DUFFY, MDt

A 56-year-old woman presented with a &month history of acne urticata, an intensely pruritic papulopustular
eruption. Skin biopsy was nondiagnostic. Touch preparations of individual lesions were remarkable for
numerous eosinophils. Peripheral blood count, bone marrow examination, and Philadelphia chromosome
positivity confirmed a diagnosis of chronic myelogenous leukemia. A serum histamine level was markedly
elevated. Treatment with hydroxyurea and antihistamines led to resolution of the skin eruption and im-
provement of the pruritus.
Cancer 56:2083-2086.1985.

C UTANEOUS LESIONS and symptoms may be the fist

manifestations of underlying malignancy. Fre-
quently, identification of the neoplasm can be made from
the gross appearance of the eruption or by histologic ex-
amination of individual lesions. Both specific and non-
specific cutaneous eruptions have been described in pa-
'
tients with hematologic malignancies. Specific eruptions
contain malignant cells of the underlying neoplasm, while
only benign appearing cells are present in the nonspecific
type. Both specific and nonspecific eruptions may be
symptomatic. Pruritus can be a symptom in both the spe-
cific and the nonspecific eruptions of hematologic malig-
nancies. Elevated levels of serum histamine, released by
malignant or inflammatory cells infiltrating the skin le-
sions, may explain their symptomatic nature. We recently
evaluated a patient with acne urticata, an intensely pruritic
papular eruption (unrelated to acne vulgaris) which her-
alded chronic myelogenous leukemia and was associated
with elevated levels of serum histamine.
Case Report
A 56-year-old woman presented to the Dermatology Depart-
ment of the Yale-New Haven Medical Center for evaluation of
a papular skin rash and severe pruritus. Her health had been
good until 6 months earlier when, following an upper respiratory
infection, she noted numerous pruritic papules on her chest and
abdomen. During the next several weeks, involvement extended
to her entire trunk and proximal extremities. Initial evaluation
failed to reveal a diagnosis. Treatment with topical steroids, an-
tihistamines, and lindane failed to produce improvement. Results
of skin biopsies 3 months prior to admission showed focal fol-
From the Departments of *Dermatology and tlnternal Medicine, Yale
University School of Medicine, New Haven, Connecticut.
Address for reprints: Paul A. Lucky, MD, Department of Dermatology,
University of Cincinnati College of Medicine, 231 Bethesda Avenue,
Cincinnati, OH 45267.
Accepted for publication January 2, 1985.
liculitis and dermatitis. Because of persistent symptoms and
continued extension of the eruption, the patient was treated with
50 mg of prednisone daily, and both the skin lesions and the
pruritus began to resolve. However, as the steroid dose was ta-
pered over 2 weeks, new papulopustules and increased pruritus
recurred. During the next several months, the patient had a total
of four courses of oral prednisone, each with initial diminution
of skin lesions and pruritus but exacerbation of the eruption
and pruritus when the prednisone was stopped. Results of repeat
biopsies during the exacerbations showed variably, edema in the
dermis with a sparse, mixed inflammatory cell infiltrate and skin
with intraepidermal pustule formation and chronic dermatitis.
Immunofluorescence results were negative. The patient was re-
ferred to the Dermatology Department of the Yale-New Haven
Medical Center when her symptoms again flared following taper
of oral prednisone from 80 mg daily.
Cutaneous examination revealed numerous discrete ery-
thematous 3 to 4 mm papules, vesicles and pustules on the trunk,
neck, scalp and extremities (Fig. I). The palms, soles, face and
mucosal surfaces were spared. Both follicular and nonfollicular
lesions were seen. There was evidence of acute and chronic ex-
coriation. The tops of many lesions had been sheared off while
others were covered with hemorrhagic crusts. The patient was
afebrile and the remainder of the physical examination was
within normal limits. Specifically, there were no palpable masses
or enlarged lymph nodes. Spleen size was normal.
Laboratory studies on admission included a leukocyte count
of 24,000 with 40% neutrophils, 23%band forms, 9%lympho-
cytes, 4% eosinophils, 2% basophils, 17% metamyelocytes, 4%
myelocytes, 1% promyelocytes, and 1% blasts. LDH was 1,240
(normal, 200-600). The remainder of the S M A 20 was normal.
PT, PTT, VDRL, urinalysis, EKG and chest x-ray results were
negative or within normal limits. Skin biopsies of both papules
and pustules were done. These demonstrated mild epidermal
edema with eosinophilic spongiosis, mature keratinocytes, and
an intact basal layer. Foci of leukocytes were seen in the lower
portion of the keratin layer in one specimen. In another, a large
subcorneal and intraepidermal pustule was seen. A loose peri-
vascular cellular infiltrate in the mid- and deep dermis consisted
of lymphocytes and a large number of eosinophils. Direct im-

2083
2084 CANCEROctober 15 1985
FIG. 1. Typical lesions of acne urticata. Numerous 3-4 mm erythematous papules, pustules and vesicles were present in a generalized distribution,
sparing only the palms, soles, face and mucosal surfaces.
munofluorescence studies revealed granular deposits of C3 in
dermal blood vessels. There was no staining for IgG, IgM, or
IgA. Serum was negative for intercellular antibodies and for an-
tibodies to basement membrane. A touch preparation,’ stained
with Wright’s stain, demonstrated a large number of eosinophils.
No blast forms were seen in the skin biopsy specimens or in the
touch preparation. Cultures of the skin pustules were negative
for bacterial growth. A bone marrow aspiration and biopsy
showed a hypercellular marrow with panmyelosis and increased
numbers of eosinophils but not basophils (Fig. 2). Liver-spleen
scan was normal. Leukocyte alkaline phosphatase was 1 (nor-
mal). Chromosome analysis demonstrated presence of the Phil-
adelphia chromosome. A serum histamine was 98 & I 0 0 ml
(normal, 3-9).
A diagnosis of chronic myelogenous leukemia was made.
Treatment with hydroxyurea, I g daily, was begun, increasing
to 1.5 g daily after 1 week. Clearing of the papules occurred
gradually over a 4-week interval after beginning hydroxyurea.
Pruritus was controlled with diphenhydramine hydrochloride
25 to 50 mg every 4 hours as needed. After several months the
patient developed a relative leukopenia and the hydroxyurea
dose was adjusted according to the leukocyte count. When the
hydroxyurea dose was reduced to less than 1 g daily, the lesions
of acne urticata recurred. Cimetidine 300 mg 3 times daily was
then added to the diphenhydramine hydrochloride to control
pruritus. Subsequently, the patient had had several flares on
Vol. 56
reduced doses of hydroxyurea. These occurred with only mildly
(approximately 13,000) elevated leukocyte counts and no ba-
sophilia. Serum histamine level afier three months of treatment
had decreased to 29 j@100 ml.
Discussion
A variety of skin rashes and cutaneous symptoms occur
in patients with malignancies. Specific (malignant) infil-
trates occur in 10% to 20% of patients with leukemia or
lymphoma and are generally asymptomatic. However,
Czarnecki el uL3reported four patients with “pruritic spe-
cific cutaneous infiltrates.” These patients all experienced
severe pruritus, and biopsy specimens from each con-
tained abnormal mononuclear cells. Histamine levels were
not reported.
Nonspecific (nonmalignant) cutaneous manifestations
of leukemia and lymphoma are more common than spe-
cific skin lesions and are reported to occur in 5% to 50%
of patients. They include purpura, exfoliative erythro-
derma, erythema multiforme, recurrent infection, pyo-
derma gangrenosum, urticaria, hyperpigmentation, pru-
ritus, and morbilliform eruptions.
Myelomonocytic leukemia is reported to have more
No. 8 ACNEURTICATA AND CHRONIC MYELOGENOUS
LEUKEMIA
FIG. 2. Bone marrow aspirate showing a hypercellularmarrow with panmyelosis. Myeloid predominance with eosinophilia is evident. Morphologically
consistent with chronic myelogenous leukemia. (original magnification MOO).
cutaneous involvement, both specific and nonspecific,
than other forms of leukemia. Peterson and Jarratt’ re-
ported a man with myelomonocytic leukemia in whom
pruritus had been present for 7 years and dermal nodules
for 4 years before a diagnosis could be made. Histology
of the cutaneous nodules was benign.
Kaposi6 coined the term “acne urticata” to describe a
widespread and pruritic papular eruption composed of
pale red wheal-like vesiculopustules. It is a distinct clinical
entity, unrelated to acne vulgaris or other acneiform
eruptions. Individual lesions consist of an urticarial papule
capped by a small vesicle or pustule. The lesions of acne
urticata appear in crops, initially on the face and on the
extensor surfaces of the extremities. They may become
generalized and are often tender. Crusting occurs after
excoriation, leaving a delicate scar and hyperpigmenta-
tion. Kaposi’s cases were chronic and were not associated
with systemic diseases.
Subsequently, numerous case reports of acne urticata
appeared in the German literature. These were reviewed
by Weidman and K l a ~ d e rIn. ~the majority of cases, acne
urticata was associated with polycythemia Vera and was
- Brydon et a!. 2085
referred to as acne urticata polycythemica. However, in
others no underlying cause could be identified. Gans’
found that the leukocytes in the pustules of acne urticata
polycythemica contained granules which stained with ox-
idase, and concluded that they belonged to the myeloid
series. This observation was confirmed by Weidman and
K l a ~ d e r .However,
~ Andrews? who reported the first
American case of acne urticata polycythemica, found only
a nonspecific inflammatory reaction with large numbers
of polymorphonuclear leukocytes on histologic exami-
nation of a papulopustule. Baxter and Lockwood’’ sub-
sequently described a patient with acne urticata whose
skin biopsy demonstrated eosinophil exocytosis and peri-
vascular infiltration.
Bluefarb and Caro4 and Bluefarb” noted that pruritus
and “prurigo-like papules” are seen relatively commonly
in lymphoma and less so in leukemia. However, of the
nonspecific cutaneous lesions in lymphocytic leukemia,
prurigo-like papules are the most frequent. They are less
common in myelocytic leukemia. The lesions described
by Bluefarb as prurigo-like papules are identical to Ka-
posi’s acne urticata:
2086 CANCEROctober I5 1985
The papules are numerous, “pinhead” to “split
pea” size, round or conical in shape, firm to the
touch, pink to rose in color, edematous and pruritic
with a deep-seated vesicle on the summit which is
scratched off and replaced by a crust. Occasionally
these papular lesions have a true bright red urticaria1
inflammatory halo, but they may be semitranslucent,
yellowish red and waxy in appearance.”
Such lesions are generally limited to the trunk and ex-
tremities and occur in crops, with pruritus increasing with
each new crop. Histologically, there is a periappendageal
round cell infiltrate with epidermal thickening and vesicle
formation in the superficial layers of the dermis. The de-
scriptions given by both Kaposi6 and Bluefarb and Caro4
closely fit our patient’s lesions. Of note is that Bluefarb
and Caro made no mention of eosinophils and did not
report histamine levels.
Basophilic transition of chronic myelocytic leukemia,
although unusual, has been reported. Basophils can release
histamine and histamine levels in patients with basophilia
are frequently elevated. Youman et a1.l’ described a pa-
tient with chronic myelocytic leukemia who developed
severe histamine related symptoms. Blood and serum lev-
els of histamine were elevated. They pointed out that al-
though total blood histamine is usually increased in pro-
portion to the absolute number of basophils, symptoms
of hyperhistaminemia are rare. Rosenthal ef al.I 3 reported
two patients with chronic myelocytic leukemia who de-
veloped an accelerated phase of the disease with marked
basophilia and hyperhistaminemia. Wheezing, urticaria,
and peptic ulcer disease were attributed to the hyperhis-
taminemia. However, the absolute basophil count and
the histamine level were not clearly correlated in these
two patients, although both values were abnormal. Two
additional patients with chronic myelocytic leukemia who
underwent basophilic transformation were reported by
Ni~senblatt.’~ One had symptoms of hyperhistaminemia
but histamine levels were not measured. The other de-
veloped cutaneous nodules, which on biopsy showed a
diffuse dermal infiltrate of myeloblasts as well as mature
and immature eosinophils. Excess basophils were not
present in the biopsy material.
Our patient had acne urticata related to chronic my-
elogenous leukemia. Numerous eosinophils were present
on a touch preparation of these papules and eosinophilic
spongiosis was present on skin biopsy. There were no
Vol. 56
myelocytes or myeloblasts seen on either the touch prep-
aration or the biopsy. Total peripheral eosinophil count
was only 4%. There was no evidence for hypereosinophilic
syndrome,” eosinophilic leukemia,I6or basophilic trans-
formation of chronic myelocytic leukemia.” The total
peripheral basophil count was only 2%. The source of the
elevated histamine in this patient is uncertain, especially
since there was no significant increase in basophils or mast
cells, which are generally believed to be the major sources
of histamine. Therapy with hydroxyurea and H 1 and H2
blockers resulted in regression of the lesions of acne ur-
ticata and diminution of the symptoms of hyperhista-
minemia. Although acne urticata may be a nonspecific
cutaneous finding, patients with these lesions should be
investigated for chronic myelogenous leukemia.
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