Actas Dermosifiliogr. 2009;100:235-48
CLInICAL SCIEnCE LEttERS
Fat Embolism Syndrome: a Condition Unfamiliar
to the Dermatologist
P. Hernández-Bel,a J. López,a E. Rodríguez-Vellando,b B. Collado,c I. Febrer,a and V. Alegrea
aServicio de Dermatología, Consorcio Hospital General Universitario de Valencia, Spain
bServicio de Traumatología, Hospital Universitario La Fe, Valencia, Spain
cServicio de Anestesiología y Reanimación, Consorcio Hospital General Universitario de Valencia, Spain
To the Editor: urinary sediment. Cerebral CT was normal and the chest
The fat embolism syndrome was described by Zenker radiograph showed multiple, peripheral, focal opacities in
in 1861,1 although the triad of confusional state, dyspnea, both lung fields.
and petechiae had already been mentioned in the German The clinical course was favorable and the patient was
literature by Von Bergman.2 Despite being described more discharged from intensive care after 10 days and from the
than 100 years ago, the diagnosis and specific treatment hospital 2 weeks later.
of this syndrome are still a subject of debate. With the Fat embolism occurs in patients with long-bone
2 cases presented here, we aim to draw attention to a
dermatological disorder which is widely discussed in the
medical and surgical literature but which is unfamiliar to
The first patient was an 18-year-old man who had
suffered a motorbike accident and presented a major lung
contusion and multiple long-bone fractures (Figure 1).
The fractures were immobilized with plaster casts and the
patient was admitted to hospital for routine surgery. He
was asymptomatic for 48 hours, but before the surgical
intervention, small papules a few millimeters in diameter
appeared; they were of reddish color, did not blanch on
pressure, and were distributed over the anterior aspect
of the thorax, base of the neck, and conjunctivae, and
in the axillas (Figure 2). This was followed by a rapid
onset of neurological signs, consisting of temporospatial
Figure 1. Case 1.
disorientation and clouding of consciousness, and acute Diaphyseal fracture of
respiratory failure. The chest radiograph showed bilateral the right femur.
opacities in both lung fields that were not present at
the time of admission. No relevant findings except for
mild thrombocytopenia were reported in the additional
studies performed—complete blood count, biochemistry,
coagulation, urinary sediment, and cerebral computed
tomography (CT). Despite intensive supportive measures,
the patient died a few hours later.
The second patient was a 27-year-old man, also victim
of a motorcycle accident. He presented fractures of the
right femur and left radius and ulna, and underwent
surgical osteosynthesis. After being asymptomatic for 48
hours, he developed fever of up to 39°C associated with
psychomotor agitation, severe acute respiratory failure,
and pinpoint petechial lesions in the axillas and around
the base of the neck. Figure 2. Case 1.
Petechial lesions with
The complete blood count revealed anemia of 9.5 g/dL a typical distribution
and thrombocytopenia of 98 ! 109/L; biochemistry and 48 hours after the
coagulation were normal. Lipiduria was observed in the injury.
Clinical Science Letters
fractures or during orthopedic procedures.3 Fat present early diagnosis of the condition and the initiation of
in the bone marrow is released, causing embolization of appropriate therapeutic measures can reduce the number
the capillary vessels in the lung parenchyma and in the of complications and improve the prognosis.8 Mortality is
peripheral circulation.4 Fat embolism can also occur in currently around 5%-10%.1,5,10
other nontraumatic disorders such as pancreatitis and The skin lesions can sometimes appear before other
sickle cell anemia, though this is rare.3 The presence clinical manifestations. The presence of petechiae
of a fat embolism is a relatively common finding and with a characteristic distribution, in an appropriate
is usually asymptomatic. However, a small number of clinical context, should therefore make us think of this
patients develop serious signs and symptoms as a result disorder.
of organ dysfunction that typically involves the skin,
central nervous system, and lungs; the term fat embolism
syndrome is reserved for these cases. The incidence of Correspondence:
Pablo Hernández Bel
this syndrome is estimated at 0.5% of long bone fractures, Servicio de Dermatología
though the majority of cases are not reported, and remain Consorcio Hospital General Universitario de Valencia
Avda. Tres Cruces, s/n
undetected in the context of a complex clinical situation.1,5 46014 Valencia, Spain
Usually, after being asymptomatic for a period of 2 or firstname.lastname@example.org
3 days (lucid interval), the patient develops the typical
clinical triad of respiratory failure, cerebral dysfunction, Conflicts of interest
and petechiae.3,6,7 The petechiae appear in crops and with The authors declare no conflicts of interest.
a typical distribution in the axillas and over the base of
the neck, shoulders, anterior chest wall, and conjunctivae,
following the path of the arterial branches of the arch of References
the aorta. They almost never affect the face or posterior
aspect of the body. Disseminated petechiae may be 1. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat
associated with more severe cerebral and pulmonary embolism syndrome: A 10-year review. Arch Surg.
dysfunction.3,5,7,8 These patients can also develop fever, 2. Von Bergman EB. Ein fall tod licher fetenbolic. Berklin
anemia, thrombocytopenia, renal failure, jaundice, and Wochenschl. 1873;10:385-7.
tachycardia.8 3. Georgopoulos D, Bouros D. Fat embolism syndrome: cli
The diagnosis is clinical and requires a high degree of nical examination is still the preferable diagnostic method.
suspicion. Gurd, in 1970, proposed a series of diagnostic Chest. 2003;123:982-3.
criteria (Table).9 This disorder often passes unnoticed due to its 4. Roca J, Ruiz J. Enfermedades vasculares del pulmón. In:
transitory nature and the lack of specificity of some signs.1,10 Farreras P, Rozman C, Editors. Medicina Interna. 15th ed.
Madrid: Elsevier; 2005. p. 836.
The fat embolism syndrome is a serious condition 5. Kaplan RP, Grant JN, Kaufman AJ. Dermatologic features of
that can sometimes follow a fulminant course. An the fat embolism syndrome. Cutis. 1986;38:52-5.
6. McIntyre K, French S, Rose TH, Byrick R. Case report:
Acute postoperative neurological impairment from fat
table. Gurd Diagnostic Criteria embolism syndrome. Can J Anaesth. 2007;54:296-300.
7. Pollock JL. Skin signs of fat embolism. Arch Dermatol.
Central nervous system depression 8. Franks A. Alteraciones cutáneas en la enfermedad
Petechiae cardiopulmonar. In: Fitzpatrick T, Editor. Dermatology in
General Medicine. 5th ed. Madrid: Panamericana; 2001. p.
Tachycardia (>120 beats per minute)
9. Gurd A. Fat embolism: an aid to diagnosis. J Bone Joint Surg.
Fever (temperature > 39oC)
Unexplained anemia 1970;52B:732-7.
Thrombocytopenia (platelet count >15 ! 109/L) 10. Talbot M, Schemitsch EH. Fat embolism syndrome: history,
definition, epidemiology. Injury. 2006;37:S3-S7.
236 Actas Dermosifiliogr. 2009;100:235-48
Clinical Science Letters
tongue Ulcer as a Manifestation of temporal Arteritis
S. Córdoba,a D. Martínez,a L. Martín,b and J.M. Borbujoa
Servicio de Dermatología and bServicio de Anatomía Patológica, Hospital Universitario de Fuenlabrada, Madrid, Spain
To the Editor: tongue, swallowing, and speaking. On examination, there
Giant cell arteritis or temporal arteritis (TA) is the was a large, well-defined, deep, excavated ulcer with a clean
most common systemic vasculitis in adults.1 Histologically base and that was not infiltrated on palpation (Figure 2); it
there is a lymphocytic-monocytic panarteritis with the was very painful.
formation of granulomas and giant cells. There is patchy On a repeat blood test, the ESR had risen to 88 mm/h,
involvement of medium and large arteries, particularly with no other abnormalities.
the extracranial branches of the carotid artery and, more Biopsy of the tongue lesion showed a deep ulcer that
specifically, the temporal artery. reached the skeletal muscle tissue, with fibrosis and images
The clinical presentation of TA is variable, with multiple, of myocyte necrosis, suggestive of ischemia (Figure 3).
nonspecific symptoms in elderly patients, particularly
women, who initially present fever, asthenia, weight loss,
headache, unpredictable joint and muscle pain, stiffness,
and polymyalgia rheumatica.1-7 Up to a third of patients
develop visual symptoms. Loss of vision, sometimes bilateral
and irreversible, is the main complication of this condition
and it can sometimes be the first symptom. The alterations
in the blood tests in TA can also be relatively nonspecific,
with normocytic-normochromic anemia, elevated alkaline
phosphatase, and a raised erythrocyte sedimentation rate
(ESR).1-7 Up to 40% of patients develop atypical clinical
manifestations such as respiratory symptoms, pyrexia
of unknown origin, aortic aneurysms, or digestive tract,
neurological, or skin disorders.1
We present the case of a 91-year-old woman with a past
history of systemic hypertension, congestive cardiac failure,
and atrioventricular block for which a pacemaker had
been implanted. She came to the emergency department Figure 1. Temporal artery with a thickened wall and a moderate
with a 48-hour history of bilateral loss of vision, with no inflammatory infiltrate in the media and adventitia. Hematoxylin-
accompanying symptoms. eosin ×4.
On physical examination there was asymmetric,
unreactive, bilateral mydriasis with changes suggestive of
ischemic optic neuritis on funduscopy.
The blood test performed in the emergency department
revealed a normocytic anemia (hemoglobin, 10.7 g/dL)
and an ESR of 23 mm/h. Cerebral computed tomography
showed no relevant abnormalities. On a suspicion of TA,
biopsy of the temporal artery was performed and treatment
was started with intravenous methylprednisolone at a dose
of 250 mg every 6 hours.
Histological study of the artery showed a thickened
wall with a moderate chronic inflammatory infiltrate
in the media and adventitia of the vessel, composed of
lymphocytes, histiocytes, occasional eosinophils, and
occasional images suggestive of giant cells (Figure 1).
Two days after starting the treatment,the patient presented Figure 2. Very painful ulcer on the right side of the tongue;
intense pain in the tongue, leading to difficulty moving the the lesion was not infiltrated on palpation.
Actas Dermosifiliogr. 2009;100:235-48 237
Clinical Science Letters
severity, and it occurs in a subgroup of older patients with
a higher incidence of loss of vision and a mortality of up
to 40%. Still less common is involvement of the tongue,
in the form of pain, stiffness, ulceration, or extensive ne-
When the diagnosis is suspected, TA must be treated
rapidly to avoid irreversible complications, particularly
complete loss of vision. TA usually responds well to high
doses of corticosteroids. The ischemic disorders, including
those of the skin, can appear at any time in the course of
the disease, particularly during the tapering of steroid treat-
ment;6 these patients must therefore remain on treatment
for long periods, sometimes for years or even for life.
TA must be included in the differential diagnosis of
tongue disorders in elderly patients with heterogeneous
Figure 3. Deep ulcer that reached the muscle tissue, and a
clinical presentations with multiple, nonspecific symp-
neutrophilic inflammatory infiltrate. Hematoxylin-eosin, ×20. toms with no other apparent cause.
Intravenous, high-dose corticosteroid treatment and Susana Córdoba Guijarro
Servicio de Dermatología
analgesia were maintained, and there was a progressive Hospital de Fuenlabrada
reduction in the size of the ulcer on the tongue, leading to C/ Camino del Molino, 2
28942 Fuenlabrada, Madrid, España,
complete re-epithelialization. However, the loss of vision email@example.com
The diagnosis of TA can sometimes be difficult as the Conflicts of interest
early symptoms are nonspecific. Age is the principal risk The authors declare no conflict of interest
factor; the disease is virtually unknown below the age of
50 years, and the incidence then gradually increases—1.5
per 100 000 population in the sixth decade of life, 20.7 References
per 100 000 population in the eighth decade.1 The most
1. Hellmann DB. Temporal arteritis, a cough, toothache and
common manifestation is unilateral headache, particularly
tongue infarction. JAMA. 2002;287:2996-3000.
affecting the temporal region. The abnormalities of the 2. Zachariades N, Skoura C, Spanous A, Machera H. Temporal
temporal artery, such as thickening, pain on palpation, or arteritis: report of a case. Oral Surg Oral Med Oral Pathol
a reduction or absence of the pulse not justified by other Oral Endod. 2006;102:192-7.
causes such as arteriosclerosis, are considered diagnostic 3. Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend
criteria. The ESR is almost always raised in TA, and can WP, Calabrese LH. The American College of Rheumatology
reach over 100 mm in some cases.2 However, the ESR is 1990 criteria for the classification of giant cell arteritis.
Arthritis Rheum. 1990;33:1122-8.
below 50 mm in up to 10% of patients, and even below 30
4. Campbell FA, Clark C, Holmes S. Scalp necrosis in temporal
mm in 4% of cases,1,5 as occurred in our patient. Biopsy arteritis. Clin Exp Dermatol. 2003;28:488-90.
of the temporal artery usually confirms the diagnosis, al- 5. Monteiro C, Fernandes B, Reis J, Tellechea O, Freitas J,
though false negatives occur in up to 5%-10% of cases due Figueiredo A. Temporal arteritis presenting with scalp ulce-
to the patchy nature of the histological changes, making a ration. JEADV. 2002;16:615-7.
second biopsy or bilateral biopsies necessary.2 The inflam- 6. Goicochea M, Correale J, Bonamico L, Domínguez R, Bagg
matory changes in the artery can persist for weeks after E, Famulari A. Tongue necrosis in temporal arteritis. Heada-
starting treatment.1 7. Biebl MO, Hugl B, Posch L, Tzankov A, Weber F, Perkmann
Dermatological abnormalities are uncommon in TA. R, et al. Subtotal tongue necrosis in delayed diagnosed giant-
Necrosis of the scalp is the most commonly reported cu- cell arteritis: a case report. Am J Otolaryngol. 2004;25:
taneous sign.4,5 It appears that this could be a marker of 438-41.
238 Actas Dermosifiliogr. 2009;100:235-48
Clinical Science Letters
Extramammary Paget Disease: Report of 2 Cases treated by
Mohs Micrographic Surgery
M. Gutiérrez-Pascual,a E. Gómez-de la Fuente,a F.J. Vicente-Martín,a and F. Pinedo-Moraledab
Servicio de Dermatología, bServicio de Anatomía Patológica, Hospital Fundación de Alcorcón, Alcorcón, Madrid, Spain
To the Editor:
Extramammary Paget disease (EPD), first described by
Crocker1 in 1889, is a rare intraepithelial neoplasia of re-
gions of the skin rich in apocrine glands. The lesions pres-
ent clinically as erythematous scaly or slightly pruriginous
plaques, and histological studies show cells with large cyto-
plasm and prominent nucleoli throughout the epidermis. In
immunohistochemical studies they test positive for carci-
noembryonic antigen (CEA), epithelial membrane antigen
(EMA), and high molecular weight cytokeratins—findings
that allow differential diagnosis from Bowen disease or
pagetoid melanoma. The histogenesis of EPD is the subject
of debate, with suggestions that it could arise from pluripo-
tential epidermal cells with subsequent glandular differen-
tiation.2 The lesions have traditionally been described in 3
subtypes: exclusively cutaneous; with an associated under-
lying adnexal carcinoma; or with a visceral neoplasia. The Figure 1. Pearly erythematous plaque on the right axilla.
prognosis varies according to the subgroup.
We present 2 new cases of EPD treated by Mohs mi-
crographic surgery (MMS).
The patients were 2 men aged 74 and 80 years old, both
consulting for plaques, one in the axillary region and the
other in the pubic area, present for 5 months and 2 years
respectively, and refractory to treatment with topical corti-
costeroids (Figures 1 and 2). Clinically these were asymp-
tomatic, noninfiltrated erythematous plaques of a pearly
appearance. Full examination produced no evidence of
other suspicious skin lesions or local swollen lymph nodes,
and no further spread was detected. The results of skin bi-
opsies were consistent with EPD (Figure 3) with positive
immunostaining for cytokeratins 8 and 18, cell adhesion
molecule 5.2, CEA, and EMA. They tested negative for
S-100 and human melanoma black 45. Surgery was un-
dertaken by deferred CMM in 2 and 3 stages, respectively Figure 2. Scaly erythematous plaque on the pubic area.
(margins of 2 cm of perilesional tissue in the first stage).
Both patients underwent reconstruction of the postexci-
sional defect with advancement plasty and direct closure
in layers, and there were no signs of local recurrence 14 but surgical excision with wide margins or MMS are the
and 10 months later, respectively. techniques of choice when there is no association with
EPD is a rare disease where 98% of cases occur in the underlying neoplasia. MMS is a treatment option for skin
genital or anoperineal region,3 with the axillary region as tumors that includes histological monitoring of the surgi-
the most common extragenital site.4 Association with in- cal margins of the tumor prior to reconstruction. There
ternal neoplasia (12%-20%) is most common in perianal are 2 modes: conventional MMS where tissue is frozen
EPD, with rates of between 15% and 45%. and subjected to histological evaluation immediately fol-
There are no clearly established guidelines for treat- lowing surgery, and deferred MMS, where the tissue is
ment (as is also the case for diagnosis and follow-up), embedded in paraffin for later study.
Actas Dermosifiliogr. 2009;100:235-48 239
Clinical Science Letters
therapy,10 topical or oral chemotherapy, CO2 laser therapy,
or topical imiquimod.
In conclusion, despite the uncommon nature of this
disease, it must be considered in all patients presenting
slow-developing erythematous scaly plaques in areas rich
in apocrine glands. MMS has achieved good results in the
treatment of EPD with a lower rate of recurrence than
wide surgical excision, and so can be considered the treat-
ment of choice at the present time.
Figure 3. Hematoxylin-eosin staining !200 and Correspondence:
immunohistochemistry with CAM 5.2 !100. Nests and cells with
enlarged cytoplasm and prominent nucleoli in all epidermal
layers. Conflicts of Interest
The authors declare no conflicts of interest.
The most extensive series to date was published in
2004,5 and involved a retrospective cohort study of 27 References
cases of EPD treated with MMS. The study examined 19
patients with primary EPD and 8 with recurrent EPD 1. Crocker HR. Paget’s disease affecting the scrotum and penis.
following initial surgery. The recurrence rate was 16% Trans Pathol Soc Lond. 1889;40:187-91.
2. Jones RE, Austin C, Ackerman AB. Extramammary Paget’s
after 58 months of postoperative follow-up for primary disease: a critical reexamination. Am J Dermatopathol.
tumors, compared with 50% after 28 months of follow-up 1979;1:101-32.
in patients with recurrent EPD. This suggested that EPD 3. Kanitakis J. Mammary and extramammary Paget’s disease.
are more aggressive, probably due to the multicentric loca- JEADV. 2007;21:581-90.
tion of these recurrent tumors. 4. Siesling S, Elferink MA, Van Dijck JA, Pierie JP, Blokx WA.
The more extensive second series of EPD treated with Epidemiology and treatment of extramammary Paget disease
MMS6 included 95 patients—80 treated with wide surgi- in the Netherlands. Eur J Surg Oncol. 2007;33:951-5.
5. Hendi A, Brodland DG, Zitelli JA. Extramammary Paget’s
cal excision and 15 with MMS. Statistically significant re- disease: surgical treatment with Mohs micrographic surgery.
sults were obtained after a period of follow-up of between J Am Acad Dermatol. 2004;51:767-73.
24 and 65 months, with recurrence of 22% for conven- 6. O’Connor WJ, Lim KK, Zalla MJ, Gagnot M, Otley CC,
tional surgery compared with 8% for MMS. Nguyen TH, et al. Comparison of Mohs micrographic sur-
According to published data, recurrence with MMS gery and wide excision for extramammary Paget’s disease.
ranges from 8% to 26%, compared with 33% to 60% for Dermatol Surg. 2003;29:723-7.
7. Appert DL, Otley CC, Phillips PK, Roenigk RK. Role of
wide surgical excision (3-5 cm margins of healthy per-
multiple scouting biopsies before Mohs micrographic sur-
ilesional tissue). However, recurrence with MMS may be gery for extramammary Paget’s disease. Dermatol Surg. 2005;
higher than 50% when dealing with a recurrent tumor.5 31:1417-22.
Adjuvant lymphadenectomy in not routinely recom- 8. Fernández-Guarino M, García-Morales I, Harto A, Montull
mended unless there are palpable lymph nodes5 as in- C, Pérez García P, Jaén P. Terapia fotodinámica: nuevas indi-
creased overall survival has not been demonstrated. caciones. Actas Dermosifiliogr. 2007;98:377-95.
When MMS cannot be used, various other techniques 9. Misas JE, Cold CJ, Hall FW. Vulvar Paget’s disease: fluo-
rescein-aided visualization of margins. Obstet Gyne-
have been tried in an effort to determine the tumor mar-
gins preoperatively, including multiple scouting biopsies,7 10. Besa P, Rich TA, Delclos L, Edwards CL, Ota DM, Whar-
photodynamic mapping,8 and fluorescein-aided visualiza- ton JT. Extramammary Paget’s disease of the perineal skin:
tion.9 When complete excision is not possible other al- role of radiotherapy. Int J Radiat Oncol Biol Phys.
ternatives are described in the literature, including radio- 1992;24:73-8.
240 Actas Dermosifiliogr. 2009;100:235-48
Clinical Science Letters
Intertriginous Rash Caused by Pegylated Liposomal
B. Monteagudo,a F.J. Afonso-Afonso,b M. Cabanillas,a and M.M. Used-Aznarc
aServicio de Dermatología, bServicio de Oncología, cServicio de Anatomía Patológica, Complejo Hospitalario Arquitecto Marcide-Novoa Santos,
Ferrol, A Coruña, Spain
To the Editor:
Doxorubicin is a chemotherapy agent of the anthracy-
cline group. It is effective in many solid and hematological
tumors, although use is limited by adverse effects—above
all cardiotoxicity and myelosuppression. Use of pegylated
liposomal doxorubicin (PLD) has recently become more
common as it is effective against Kaposi sarcoma and
ovarian cancer. This form of the drug has fewer adverse ef-
fects, but marked cutaneous toxicity still limits the dosage
prescribed.1 Common cutaneous reactions include palmo-
plantar erythrodysesthesia (“hand-foot” syndrome)2,3 and
stomatitis, and a diffuse follicular eruption or intertrigi-
nous rash is also highly characteristic of PLD use.4,5
We present a new case of an intertriginous rash caused Figure 1. Scaly, erythematous and erosive areas on the left
by PLD in a 53-year-old woman with a history of clear axilla.
cell ovarian cancer and histopathology findings that in-
dicate epidermal dysmaturation. Only 3 similar cases in-
cluding histopathological studies have been found in the senting hyperpigmented plaques with scaly erythematous
dermatological literature.6-8 erosive and crusty areas on the axillas, groin, and waist
The patient was a 53-year-old woman with a history (Figure 1).
including depression, fibrocystic breast disease, lumbar A biopsy was taken from one of the lesions in the left
and sciatic pain from herniated discs L4-L5 and L5-S1, axilla showing discrete hyperkeratosis and papillomatosis
cholecystectomy, and appendectomy. She was admitted of the epidermis. There was a noticeable increase in size
for left popliteal deep vein thrombosis. Abdominal-pelvic of the keratinocytes in the basal layer and middle layers,
computed tomography (CT) revealed a lobulated mass with enlarged atypical nuclei, occasional double nuclei,
was observed in the pelvis minor with cancer antigen prominent nucleoli, and mitosis. Inflammatory infiltrate
(CA) 15.3 levels of 189.4 U/mL (normal values: 0.0-38.6 was present in a perivascular distribution in the middle
U/mL) and CA 125 levels of 23.5 U/mL (normal values: papillary dermis. The infiltrate consisted of lymphocytes
0.0-30.0 U/mL). A total hysterectomy, double adnexec- and scant neutrophils. This was in contact with the basal
tomy, and partial omentectomy were performed. A left layer in some areas causing discrete disruptions and even
adnexal tumor of 8 cm in diameter was found and histo- penetrated into the epidermis in small groups (Figures 2
pathology showed a poorly differentiated clear cell carci- and 3).
noma. The postsurgical thoracic abdominal and pelvic CT A diagnosis was made of intertriginous rash with in-
was normal, but CA 15.3 values of 54 U/mL were found. terphase dermatitis and epidermal dysmaturation caused
As this was a stage 1A cancer, adjuvant chemotherapy by PLD, and treatment with the drug was continued at a
was initiated with 4 cycles of paclitaxel and carboplatin, reduced dosage of 40 mg/m2. There was no recurrence of
but CA 15.3 levels rose to 72 U/mL. A further CT was the complaint following the third infusion.
normal, but the positron emission tomography showed PLD frequently causes cutaneous toxicity. The most
an area of intense uptake suggestive of an adenopathic common reaction is palmoplantar erythrodysesthesia.
conglomerate in the paraaortic region. A new course of This occurs in a third of all patients and consists of the
therapy was started with PLD 50 mg/m2 every 4 weeks. development of erythematous lesions on the palms and
Three weeks after the second cycle of PLD the patient plantar surfaces, accompanied by a sensation of dysesthe-
developed a pruriginous rash in the skin folds that was sia.2,3 There can also be a recall reaction in areas were sun-
treated with 0.1% methylprednisolone aceponate emul- burn, radiotherapy, or extravasation of cytostatic agents
sion for 10 days. The patient consulted at this point, pre- has occurred previously. Other reported effects include
Actas Dermosifiliogr. 2009;100:235-48 241
Clinical Science Letters
Although there are many reported cases of PLD in-
ducing a similar intertriginous rash,4,5 we have only
found 3 articles describing the histopathological findings
(Table).6-8 The condition is denoted "dermatitis or an in-
tertrigo-like eruption" in order to distinguish it as an in-
dependent morphological entity, even though the patho-
genic mechanism may be identical to that of "hand-foot
syndrome."5,8 Erythematous plaques appear several weeks
after the last infusion in all cases of treatment with PLD,
Figure 2. Epidermal often producing bilateral erosive, pruriginous or pain-
cytological atypia and ful areas on the axillas, groin, and areas of friction with
inflammatory infiltrate clothing. Histopathological study shows an interphase
in the dermis
reaction with epidermal dysmaturation (cytological aty-
×400). pia with apoptotic/dyskeratotic keratinocytes). Epidermal
dysmaturation often presents during treatment with other
chemotherapy agents like cyclophosphamide,10 and there
have been many cases published recently of PLD-induced
rashes with this histological pattern.7,11 As in our case, re-
ducing the drug dosage resolved the skin lesions leaving
some residual postinflammatory hyperpigmentation but
no subsequent recurrence.6-8
Benigno Monteagudo Sánchez,
C/ Alegre, 83-85, 3.ºA,
15401 Ferrol, A Coruña, Spain
Conflicts of Interest
The authors declare no conflicts of interest.
Figure 3. Apoptotic keratinocytes and inflammatory infiltrate in
the dermis (hematoxylin-eosin, ×200).
the formation of new melanotic macules, stomatitis, or a 1. Waterhouse DN, Tardi PG, Mayer LD, Bally MB. A compa
diffuse symptomatic follicular eruption predominantly on rison of liposomal formulations of doxorubicin with drug
the lateral surface of the extremities or trunk.4,5 The his- administered in free form: changing toxicity profiles.
topathology in the latter case generally shows vacuoliza- DrugSaf. 2001;24:903-20.
tion of the basal layer and a lymphocytic infiltrate in the 2. Lorusso D, Di Stefano A, Carone V, Fagotti A, Pisconti S,
Scambia G. Pegylated liposomal doxorubicin-related pal-
table. Patients With Intertriginous Rash Caused by PLD and Histopathological Study
Reference Age/Sex Cancer Intervala Site Histologic Findings
Skelton et al 6 83 years/W Ovary 21 days Axillas and groin Interphase dermatitis and apoptotic keratinocytes
English III et al7 64 years/W Ovary 11 days Axillas, side of Interphase dermatitis and apoptotic keratinocytes
breasts, and groin
Korver et al8 60 years/W Breast 14 days Axillas, groin, lower Interphase dermatitis and dyskeratotic keratinocytes
abdomen, and oral
Monteagudo et al 53 years/W Ovary 21 days Axillas, groin, and Interphase dermatitis and dyskeratotic keratinocytes
(present case) lower abdomen
a Interval between the last infusion of the drug and appearance of the rash.
242 Actas Dermosifiliogr. 2009;100:235-48
Clinical Science Letters
mar-plantar erythrodysesthesia (‘hand-foot’ syndrome). Ann 7. English III JC, Toney R, Patterson JW. Intertriginous epi-
Oncol. 2007;18:1159-64. dermal dysmaturation from pegylated liposomal doxorubi-
3. Hueso L, Sanmartín O, Nagore E, Botella Estrada R, cin. J Cutan Pathol. 2003;30:591-5.
Requena C, Llombart B, et al. Eritema acral inducido por 8. Korver GE, Ronald H, Petersen MJ. An intertrigo-like erup-
quimioterapia: estudio clínico e histopatológico de 44 casos. tion from pegylated liposomal doxorubicin. J Drugs Derma-
Actas Dermosifiliogr. 2008;99:281-90. tol. 2006;5:901-2.
4. Kim RJ, Peterson G, Kulp B, Zanotti KM, Markman M. 9. Saini A, Berruti A, Sperone P, Bitossi R, Tampellini M,
Skin toxicity associated with pegylated liposomal doxorubi- Dogliatti L, et al. Recall inflammatory skin reaction after use
of pegylated liposomal doxorubicin in site of previous drug
cin (40 mg/m2) in the treatment of gynecologic cancers.
extravasation. Lancet Oncol. 2006;7:186-7.
Gynecol Oncol. 2005;97:374-8.
10. Castaño E, Rodríguez Peralto JL, López Ríos F, Gómez C,
5 . Lotem M, Hubert A, Lyass O, Goldenhersh MA, Ingber A, Zimmermann M, Iglesias Díez L. Keratinocyte dysplasia: an
Peretz T, et al. Skin toxic effects of polyethylene glycol-coated usual finding after transplantation or chemotherapy. J Cutan
liposomal doxorubicin. Arch Dermatol. 2000;136:1475-80. Pathol. 2002;29:579-84.
6. Skelton H, Linstrum J, Smith K. Host-vs.-altered-host erup- 11. Cady FM, Kneuper Hall R, Metcalf JS. Histologic patterns
tions in patients on liposomal doxorubicin. J Cutan Pathol. of polyethylene glycol-liposomal doxorubicin-related cuta-
2002;29:148-53. neous eruptions. Am J Dermatopathol. 2006;28:168-72.
Merkel Cell Carcinoma at a Site of Vaccination
B. Monteagudo,a M. Cabanillas,a J.A. García-Rego,b and J.M. Cacharróna
Servicio de Dermatología, bServicio de Anatomía Patológica, Complejo Hospitalario Arquitecto Marcide-Novoa Santos, Ferrol, A Coruña, Spain
To the Editor: vaccine of inactive and fractionated viruses containing the
Adverse skin reactions from vaccination are very varied following antigens: A/Solomon Islands/3/2006 [H1N1]-
and can be local or generalized. Immediately after immu- like strain, A/Wisconsin/67/2005 [H3N2]-like strain, and
nization, erythema, edema, pain, and induration may occur B/Malaysia/2506/2004-like strain). His physician initially
exclusively on the site of the injection, and these disappear diagnosed an abscess caused by administration of the vac-
spontaneously. Less frequently, papules or nodules appear cine, and prescribed oral antibiotics prior to draining.
that can persist for months or even years, consisting of Examination revealed a hard and poorly defined tumor,
nonspecific granulomatous or lymphoid reactions.1,2 measuring 5 cm ×3 cm, located on the external surface of
Various tumors have also been described on the site the right arm. The tumor surface showed many violaceous
of vaccine injections: basal cell carcinoma, squamous cell dome-shaped nodules (Figure).
carcinoma, malignant melanoma, malignant fibrous his- A biopsy was taken to confirm a provisional diagnosis of
tiocytoma, dermatofibrosarcoma protuberans (including pseudolymphoma or lymphoma caused by the vaccination
the pigmented variant, Bednar tumor), dermatofibroma, and the ensuing histopathological study showed a tumoral
and marginal zone B-cell lymphoma. The delay between infiltration of the dermis by rounded monomorphic cells of
vaccination and the appearance of the tumor varies widely, medium size with scant cytoplasm, round nuclei, and small
from days in the case of lymphomas, to more than 30 years nucleoli, forming solid masses or small trabecular struc-
in many patients with basal cell carcinoma.3-5 tures. The mitotic index was high. Immunohistochemical
In this letter we report the case of an 84-year-old man study proved positive for cytokeratin 20, neuronal specific
who consulted with a tumor on the right arm that ap- enolase, chromogranin A, and chromogranin B. There was
peared a week after receiving an influenza vaccination in no immunoreactivity to protein S-100, leukocyte common
the same location. Histopathological and immunohis- antigen, CD20, CD3, cytokeratin 7, or thyroid transcrip-
tochemical studies provided the basis for a diagnosis of tion factor 1. A diagnosis of MCC was made and the pa-
Merkel cell carcinoma (MCC). tient was referred to the Oncology Department.
The patient was an 84-year-old man with a history of MCC—first described by Toker in 1972—is a rare ma-
Parkinson disease, referred to the Dermatology Depart- lignant cutaneous tumor of neuroendocrinal origin with
ment because of a fast-growing asymptomatic lesion in poor prognosis and rapid progression. It tends to pres-
the right deltoid region present for 2 months. According ent as a fast-growing nodular erythematous lesion on the
to the patient and his family, the lesion first appeared on head, neck, or limbs in people aged over 65 years.6,7
the site of the influenza vaccination received a week pre- The pathogenesis is unknown although various factors
viously during the 2007 vaccination campaign (trivalent have been implicated: a) ultraviolet radiation—a greater
Actas Dermosifiliogr. 2009;100:235-48 243
Clinical Science Letters
the development of MCC patients with a predisposition
to the disease.
Benigno Monteagudo Sánchez
C/ Alegre, 83-85, 3.ºA,
15401 Ferrol, A Coruña, Spain
Conflicts of Interest
The authors declare no conflicts of interest.
Figure 1. Poorly defined tumor 5 cm ! 3 cm in diameter, with 1. Nikkels AF, Nikkels Tassoudji N, Pierard GE. Cutaneous
multiple violaceous nodules on the surface, located on the outer adverse reactions following anti-infective vaccinations. Am J
surface of the right arm. Clin Dermatol. 2005;6:79-87.
2. Wu JJ, Huang DB, Pang KR,Tyring SK. Vaccines and immuno-
therapies for the prevention of infectious diseases having cuta-
incidence in areas exposed to sunlight in patients with a neous manifestations. J Am Acad Dermatol. 2004;50:495-528.
history of basal or squamous cell carcinoma; b) other car- 3. Reed WB, Wilson-Jones E. Malignant tumors as a late com-
cinogens—frequent occurrence in areas of irradiation, er- plication of vaccination. Arch Dermatol. 1968;98:132-5.
ythema ab igne, or following chronic exposure to arsenic; 4. Green JJ, Heymann WR. Dermatofibrosarcoma protuberans
c) immunosuppression—from treatment in a liver or heart occurring in a smallpox vaccination scar. J Am Acad Derma-
transplant setting or rheumatic diseases; and in patients
5. May SA, Netto G, Domiati Saad R, Kasper C. Cutaneous
with hematologic neoplasias or infection with the human lymphoid hyperplasia and marginal zone B-cell lymphoma
immunodeficiency virus (HIV); d) cases described in pa- following vaccination. J Am Acad Dermatol. 2005;53:512-6.
tients with congenital ectodermal dysplasia or Cowden 6. Alonso A, Daudén E, Álvarez Ruiz S, Ríos L, Fraga J, García
disease; and e) oncogenic viruses—although the role of Díez A. Placa eritematosa frontal de crecimiento rápido.
Epstein-Barr virus has not been proven.8-10 Actas Dermosifiliogr. 2005;96:264-6.
In conclusion, we present a case of MCC located at 7. Swann MH, Yoon J. Merkel cell carcinoma. Semin Oncol.
a site of vaccination. As we have encountered no simi- 8. Paradela de la Morena S, Peña C, Fonseca Capdevila E. Car-
lar cases in the literature to date—even though the target cinoma de Merkel. Piel. 2005;20:266-76.
population for anti-influenza vaccination overlaps ex- 9. Kanitakis J, Euvrard S, Chouvet B, Butnaru AC, Claudy A.
tensively with those at greater risk of developing MCC Merkel cell carcinoma in organ-transplant recipients: report
(individuals aged 65 years or older and immunodepressed of two cases with unusual histological features and literature
patients)—we believe this is a case of simple coincidence. review. J Cutan Pathol. 2006;33:686-94.
10. Shaw M, Warren S, Groben P, Gulley ML. No evidence of
However, the close temporal relationship could indicate
Epstein-Barr virus association with Merkel cell carcinoma. J
that vaccination causes a local immune alteration through Cutan Pathol. 2006;33:624-8.
an unknown pathogenic mechanism that would facilitate
Eruptive Clear Cell Acanthoma
V. Morillo,a P. Manrique,a I. Zabalza,b and J.L. Artolaa
Sección de Dermatología, bServicio de Anatomía Patológica, Hospital de Galdakao, Galdakao, Vizcaya, Spain
To the Editor: inflammatory origin, although they questioned this affirma-
Clear cell acanthoma (CCA) was described by Degos et tion 8 years later. In recent years, several authors have vindi-
al1 in 1962. They suggested that this was a benign epithelial cated the inflammatory nature of this lesion, and a number of
tumor of epidermal origin rather than a reactive hyperplasia of writers view the condition as a localized form of psoriasis.2,3
244 Actas Dermosifiliogr. 2009;100:235-48
Clinical Science Letters
Figure 1. Eruptive clear cell acanthoma on the legs. Figure 2. Multiple clear cell acanthomas on the thighs.
CCA is generally solitary and multiple forms are un-
common. However, there is one isolated description in the
medical literature of an eruptive form of the disease with
more than 400 lesions.
Our patient was a 32-year-old woman with no relevant
history, except for the presence of a crusty plaque on the
occipital zone of the scalp during adolescence that disap-
peared spontaneously several years ago. The family his-
tory included a father and brother with psoriasis. The pa-
tient consulted for the progressive appearance of multiple
erythematous papules on her legs and buttocks over the
last 20 years (Figures 1 and 2). These were of an elastic Figure 3. Acanthotic
consistency, with some slightly scaly lesions. The patient epidermis with clear
mentioned occasional bleeding when wearing tight trou- and enlarged
sers. She reported the appearance of similar papules on
the trunk and arms over the course of the last year. ×20).
A diagnosis of lichen myxedematosus was proposed
and biopsies taken of 3 papules, all with similar histo-
pathological findings. Each biopsy revealed a psoriasiform
hyperplasia with large cells and clear cytoplasm (Figure
3) that proved intensely periodic-acid-Schiff positive. The to ours in the medical literature in which a woman had
boundary with the adjacent healthy epidermis was very more than 400 lesions that appeared progressively.9
well defined in all 3 lesions. The etiology of CCA is far from established, and even
CCA is generally solitary and is most often located on Degos recognized that the neoplastic nature of the le-
the legs, although the case described by Degos et al1 was sions was still not fully confirmed 8 years after his initial
on the abdomen. The first case of multiple CCA was de- description of the condition. Since then, many authors
scribed in 19644 and some 30 articles have been published have suggested that CCA shows a psoriasiform reaction
since then. Most of the cases described were CCA patients pattern, generally on the basis of the following 3 crite-
with between 2 and 20 lesions on the legs. The lesions ria2,3,10:
sometimes appeared in association with ichthyosis, vari-
cose veins, psoriasis, or xerotic skin, although whether this 1. Many of the CCA described are located within other
is coincidental has neither been confirmed or disproved.5,6 inflammatory or reactive lesions, either stasis dermati-
There is also one very interesting case of multiple CCA tis, pilonidal cysts or psoriasis plaques.
in a mother and her 2 children, but, as far as we are aware, 2. CCA and psoriasis produce very similar histopathologi-
this is the only familial example described.7 cal findings and dermatoscopic patterns.
These 30 cases include isolated incidences of patients 3. A recent study proved that the results of immunohis-
with more than 100 lesions distributed across the trunk tochemical analysis were similar to those for the normal
and limbs.8 However, we have only found one case similar epidermis and for psoriasis.
Actas Dermosifiliogr. 2009;100:235-48 245
Clinical Science Letters
In view of the above it is possible to posit that our pa- References
tient was simply experiencing an exceptional manifesta-
tion of familial psoriasis. 1. Degos R, Delort J, Civatte J, Poiares BA.Tumeur épidermi-
que d’aspecte particulier: acanthome à cellules claires. Der-
The patient reported that private phototherapy ses-
sions several years ago had led to apparent improvements 2. Terrasa F, Saus C, Mestre F. Acantoma de células claras como
in the lesion, although they had later reappeared. We ini- forma localizada de psoriasis. Med Cutan Iber Lat Am.
tially administered broad-band UVB phototherapy with 2005;33:91-2.
no response. We then proposed PUVA treatment, but the 3. Finch TM, Tan CY. Clear cell acanthoma developing on a
patient has so far refused any further treatment. psoriatic plaque: further evidence of an inflamatory aetio-
logy? Br J Dermatol. 2000;142:842-4.
4. Delacretaz J. Acanthomes à cellules claires. Dermatologica.
5. Betti R, Bruscagin C, Inselvini E, Palvarini M, Crosti C.
Successful cryotherapy treatment and overview of multiple
clear cell acanthomas. Dermatol Surg. 1995;21:342-4.
6. Landry M, Winkelmann RK. Multiple clear cell acanthoma
and ichthyosis. Arch Dermatol. 1972;105:371-83.
7. Balus L, Carnelli T, Cristiani R. Acanthome à cellules claires
multiple et familial. Ann Dermatol Venereol. 1984;111:665-6.
8. Paz R, González R, García F. Multiple clear cell acanthomas.
9. Innocenzi D, Barduagni F, Cerio R. Disseminated eruptive
Hospital de Galdakao clear cell acanthoma: a case report with review of the litera-
Barrio Labeaga, s/n, ture. Clin Exp Dermatol. 1994;19:249-53.
48960 Galdakao, Vizcaya, Spain 10. Zedek DC, Langel DJ, White WL. Clear cell acanthoma
versus acanthosis: A psoriasiform reaction pattern lacking
Conflicts of Interest tricholemmal differentiation. Am J Dermatopathol.
The authors declare no conflicts of interest. 2007;29:378-84.
Allergic Contact Dermatitis to Hydrocortisone
as a Complication of tattoo Care
C. Laguna, V. Zaragoza, and J. de la Cuadra
Servicio de Dermatología, Hospital General Universitario de Valencia, Valencia, Spain
To the Editor: tattoo was to be completed in 2 sessions and that the up-
Many complications have been described in the con- per part was incomplete (Figure 1A). He applied Terra
text of tattooing, including various types of infection, the Cortril ointment (hydrocortisone and oxytetracycline in
appearance of tumors, granulomatous reactions, and con- petroleum jelly as excipient; Farmasierra Laboratorios) as
tact allergy.1 Allergic contact dermatitis (ACD) has been recommended by the tattooist following the tattoo session,
described in these cases in relation to some of the pig- and the skin lesions appeared a week later. The emergency
ments used, especially the red color. However, the person department prescribed Diprogenta cream (betamethasone
with the tattoo may also use many products to care for the and gentamicin; Shering Plough) and Dexa Tavegil (dex-
tattoo—corticosteroids, antibiotics, healing or antiseptic amethasone and clemastine; Novartis Consumer Health)
ointments—that may provoke ACD. We describe 2 cases and the lesions healed. Despite the recommendations, 2
of ACD from hydrocortisone use in patients who applied months later the patient decided to complete the tattoo
an ointment containing hydrocortisone recommended by and apply Terra Cortril ointment, causing the skin le-
the tattooist for the localized care of their tattoos. sions to return 2 days later (Figure 1B). Treatment with
The first patient was a 21-year-old man who attended Diprogenta once more produced a good clinical response.
the emergency department with severe eczema on the left Patch testing for contact dermatitis was performed with
leg. The lesions were located around a permanent black the Spanish Group for Research Into Dermatitis and
tattoo created 10 days previously. The patient stated the Skin Allergies (GEIDAC) standard battery—showing a
246 Actas Dermosifiliogr. 2009;100:235-48
Clinical Science Letters
table 1. Battery of Corticosteroids Used in the Skin
A B Allergy Section of the Consorcio Hospital General
Universitario de Valencia, Spain
1 Betamethasone dipropionate 0.5% pj
2 Clobetasol 17-propionate 1% pj
3 Betamethasone 17-valerate 1% pj
4 Triamcinolone acetonide 1% pj
5 Hydrocortisone 17-butyrate 1% alc
6 Alclometasone 17.21-dipropionate 1% pj
7 Dexamethasone 21-phosphate 1% pj
8 Prednicarbate 1% pj
9 Prednisolone 5% pj
10 Dexamethasone 21-acetate 1% pj
C 11 Fluocinolone 0.25% pj
12 Betamethasone base 1% pj
13 Dexamethasone base 1% pj
14 Hydrocortisone acetate 25% pj
15 Hydrocortisone 2.5% alc
16 Hydrocortisone base 25% pj
17 Triamcinolone acetonide 5% pj
18 Betamethasone 17-valerate 5% pj
Abbreviations: alc: alchohol; pj: petroleum jelly.
Figure 1. A. Eczema surrounding a tattoo located on the left calf.
The lesions appeared after the application of Terra Cortril
ointment for a week. B. Eczema following completion of the
tattoo. Symptoms recurred 2 days after application of the
ointment. C. Positive reactions to patch tests for tixocortol
pivalate, hydrocortisone, and hydrocortisone 17-butyrate.
positive reaction to tixocortol pivalate (+++D2, +++D4,
+++D7); our series of corticosteroids (Table)—testing
positive for 2.5 alcohol excipient (++D2, +++D4, +++D7)
and hydrocortisone 17-butyrate (++D2, +++D4, +++D7)
(Figure 1C); and a patch with 5% tetracycline in petro-
leum jelly—which showed no reaction.
The second patient was a 19-year-old woman who at- Figure 2. Eczema in the lumbo-sacral region that appeared
tended the Emergency department with eczematous le- several days after application of Terra Cortril.
sions in the lumbosacral region, at the site of a tattoo com-
pleted 3 days previously (Figure 2). The patient related
the inflammation to the application of the Terra Cortril
ointment recommended by the tattooist. Dexa Tavegil and with results identical to the first case: tixocortol pivalate (+
Diprogenta were prescribed with good clinical response, day 2 [D2], ++ day 4 [D4], ++ day 7 [D7]) hydrocortisone
and patch tests were performed with the standard bat- 2.5 alcohol excipient (+D2,++D4, ++D7) and hydrocorti-
tery, corticosteroids and 5% tetracycline in petroleum jelly, sone 17-butyrate (+/–D2, +D4, +D7).
Actas Dermosifiliogr. 2009;100:235-48 247
Clinical Science Letters
Although the use of topical corticosteroids is extremely ing corticosteroids in caring for damaged skin following
common, it is rare to find positive patch tests for these.2 the tattooing process. In conclusion, on the basis of our
In Spain, incidence of sensitivity to corticosteroids is less observations, we suggest tattoos be considered among the
than 1%. group of risk factors for developing contact sensitivity to
Hydrocortisone belongs to group A of the Coopman corticosteroids, in this particular case, to hydrocortisone.
classification.4 This system is based on different substitu-
tions on the D ring or in the C20-C21 position of the
lateral chain of the steroid molecule, and attempts to ex- Correspondence:
plain cross-reactions between corticosteroids. Three corti- Servicio de Dermatología
costeroids have been described as contact allergy markers: Hospital General Universitario de Valencia
Av. Tres Cruces, s/n, 46014 Valencia, Spain
tixocortol pivalate—as a group A marker; budesonide—as firstname.lastname@example.org
a group B marker; and hydrocortisone 17-butyrate—as a
Conflicts of Interest
group D marker. Allergic reactions to group C corticos- The authors declare no conflicts of interest.
teroids are extremely uncommon. Most cross-reactions
occur between corticosteroids in the same group, and also
between group A and D. In our cases cross-reaction was
observed between hydrocortisone (group A) and hydro- References
cortisone 17-butyrate (group D), however, betamethasone
and dexamethasone—both from group C—were well tol- 1. Kazandjieva J,Tsankov N. Tattoos: dermatological
complications. Clin Dermatol. 2007;25:375-82.
erated by both patients. 2. Calzado L, Ortiz-Frutos FJ, Galera C, Prado-Sánchez C,
When a corticosteroid responsible for a contact allergy Vanaclocha F. Allergic contact dermatitis caused by
is administered orally, dermatitis is reactivated in the af- 6a-methylprednisolone aceponate. Contact Dermatitis.
fected locations. Immediate reactions such as urticaria 2005;53: 62-3.
and anaphylaxis have been described, but these are un- 3. Camarasa JG. Contact allergy to corticosteroids: a challenge
common. for dermatologists. J Eur Acad Dermatol Venereol. 2001;15:
Contact allergy to corticosteroids must be suspected
4. Coopman S, Degreef H, Dooms-Goossens A. Identification
when there is no improvement in chronic dermatitis. The of cross-reaction patterns in allergic contact dermatitis from
existence of ulcers on the legs, stasis dermatitis, chronic topical corticosteroids. Br J Dermatol. 1989:121:27-34.
dermatitis, and multiple drug sensitivity are considered 5. Wilkinson SM, English JSC. Hydrocortisone sensitivity:
risk factors in developing a contact allergy to corticoster- Clinical features of fifty-nine cases. J Am Acad Dermatol.
oids.5 In our experience many patients use creams contain- 1992;27:683-7
248 Actas Dermosifiliogr. 2009;100:235-48