giornale italiano di dermatologia e venereologia

103 Pages·2014·5.14 MB·English

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OFFICIAL JOURNAL OF THE SOCIETÀ ITALIANA DI DERMATOLOGIA MEDICA,
CHIRURGICA, ESTETICA E DELLE MALATTIE SESSUALMENTE TRASMESSE (SIDeMaST)
VOLUME 149 - No. 3 - JUNE 2014
GIORNALE ITALIANO DI
DERMATOLOGIA E VENEREOLOGIA
Official Journal of the “Società Italiana di Dermatologia Medica, Chirurgica,
Estetica e delle Malattie Sessualmente Trasmesse (SIDeMaST)”
Honorary Editor Editor in Chief Assistant Editors
Mario PIPPIONE Andrea PESERICO Nicola PIMPINELLI - Pietro QuAgLINO
Honorary Members and Editorial Committee
M. Bagot (Paris, France) - L. Borradori (Bern, Switzerland) - R. Cerio (London, uK) - K. D. Cooper (Cleveland, uSA)
P. M. Elias (San Francisco, uSA) - J. Hercogova (Prague, Czech Republic) - F. Kerdel (Miami, uSA) - C. Paul (Tolouse, France)
M. R. Pittelkow (Rochester, uSA) - R. Schwartz (Newark; uSA) - W. Sterry (Berlin, germany) - E. Tschachler (Vienna, Austria)
Editorial Board
P. Amerio (Chieti) - g. Argenziano (Reggio Emilia) - A. Belloni Fortina (Padova) - N. Cassano (Bari) - A. Costanzo (Roma)
E. Cozzani (genova) - M. C. Fargnoli (L’Aquila) - F. Lacarrubba (Catania), D. Linder (Padova) - I. Neri (Bologna)
F. Rongioletti (genova) - F. Sampogna (Roma) - C. Tomasini (Torino) - M. Venturini (Brescia) - g. Zambruno (Roma)
SOCIETà ITALIANA DI DERMATOLOGIA MEDICA, CHIRuRGICA, ESTETICA
E DELLE MALATTIE SESSuALMENTE TRASMESSE (SIDeMaST)
Board of Directors
Andrea Peserico (President) - gianfranco Altomare - Emilio Berti - Sergio Chimenti - Clara De Simone
Alberico Motolese - Aurora Parodi - giovanni Pellacani
Nicola Pimpinelli - Carlo Pincelli - Anna Virgili
Managing Editor
Alberto OLIARO
This journal is peer reviewed and is indexed by: embase, pubmed/medLiNe, science Citation index expanded (scisearch), scopus
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GIORNALE ITALIANO DI
DERMATOLOGIA E VENEREOLOGIA
Vol. 149 June 2014 No. 3
CONTENTS
DRUG ERUPTIONS - Part II 317
Guest Editors: G. BORRONI, C. TOMASINI Tyrosine kinase inhibitors: muco-cutaneous side
effects at the microscope
281 Grasso V., Vassallo C., Croci G., Brazzelli V.
Acute generalized exanthematous pustulosis: report of
five cases and systematic review of clinical and histo-
329
pathological findings
Vassallo C., Derlino F., Brazzelli V., D’Ospina R. M., Thalidomide-induced granuloma annulare
Borroni G. Ferreli C., Atzori L., Manunza F., Pau M., Caddori A.
335
291
ORIGINAL ARTICLES
Histopathologic spectrum of Drug Reaction with
Topical lactoferrin can improve stable psoriatic pla-
Eosinophilia and Systemic Symptoms (DRESS): a dia-
que
gnosis that needs clinico-pathological correlation
Saraceno R., Gramiccia T., Chimenti S., Valenti P., Pietropaoli
Borroni G., Torti S., Pezzini C., Vassallo C., Rosso R.,
M., Bianchi L.
D’Ospina R. M., Tomasini C., Brazzelli V.
341
301
Clinically and/or histologically pigmented poromas
Drug-induced lupus erythematosus in Caucasian patients
Marzano A. V., Tavecchio S., Menicanti C., Crosti C. Betti R., Bombonato C., Cerri A., Moneghini L., Abramo P.,
Menni S.
311 347
Inflammatory/infectious cutaneous side effects of
In vivo and in vitro evaluation of topical formu-
biological drugs in patients with psoriasis: a general
lations containing physiological lipid mixture for
review with personal data
replacement of skin barrier function
Rongioletti F., Burlando M., Parodi A.
Barba C., Parra J. L., Coderch L., Semenzato A.
Vol. 149 - No. 3 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA XV
CONTENTS
355 372
Psychopathology and eating disorders in patients Lymphangiomas arising on lymphedema: first step of
with psoriasis malignant development
Crosta M. L., Caldarola G., Fraietta S., Craba A., Benedetti C., Lo Schiavo A., Brancaccio G., Romano F., Caccavale S.
Coco V., Janiri L., Rinaldi L., De Simone C.
374
363 A rare association between neurofibromatosis type 1
and vulvar sarcoma
CASE REPORTS Miraglia E., Pecorella I., Persechino F., Visconti B., Calvieri S.,
Periungual pyogenic granulomas due to topical taza- Giustini S.
rotene for nail psoriasis
Piraccini B. M., Venturi M., Patrizi A.
376
A clinical case of cutaneous silica granuloma
Onesti M. G., Fino P., Amorosi V., Piro F., Pedace D., Carella
367
S., Latini C.
Multiple skin ulcers due to Serratia marcescens in a
immunocompetent patient
378
Carlesimo M., Pennica A., Muscianese M., Bottoni U.,
Abruzzese C., Giubettini M., Pranteda G., Pranteda G. Merkel cell carcinoma of the lower limb
De Paola M., Poggiali S., Miracco C., Pisani C., Batsikosta A.,
Bilenchi R.
371
381
CORRESPONDENCE
A case of superimposed segmental giant melanocytic Yellow urticaria in a patient with hepatic cirrhosis
nevus Chiba T., Hayashi F., Shinmura M., Kiyomatsu M., Tatematsu
Piccolo V., Russo T., Picciocchi R., Ametrano O., Moscarella E. S., Nakao M., Furue M.
XVI GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA June 2014
Anno: 2014 Lavoro:
Mese: June titolo breve: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS
Volume: 149 primo autore: VASSALLO
No: 3 pagine: 281-90
Rivista: GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA
Cod Rivista: G ITAL DERMATOL VENEREOL

DRUG ERUPTIONS - Part II
Guest Editors: G. Borroni, C. Tomasini
G ITAL DERMATOL VENEREOL 2014;149:281-90
Acute generalized exanthematous pustulosis: report of five cases
and systematic review of clinical and histopathological findings
C. VASSALLO, F. DERLINO, V. BRAZZELLI, R. M. D’OSPINA, G. BORRONI
Acute generalized exanthematous pustulosis (AGEP) is a rare, Dermatology Unit, Department of Clinical‑Surgical
drug-related pustular eruption usually starting from folds Diagnostic and Pediatric Sciences, University of Pavia
with edema and erythema and with subsequent spreading. Policlinico San Matteo IRCCS Foundation, Pavia, Italy
Clinically AGEP is characterized by the sudden appearance of
dozen of sterile, non follicular, small pustules on erythematous
and edematous skin. Mild non erosive mucosal involvement, of oedematous erythema, associated with peripheral
mostly oral, may sometimes occur. Fever, neutrophilia and pe-
blood leukocytosis. In 1968 Baker and Ryan identi-
ripheral blood eosinophilia (in a third of patients) are present.
fied 5 patients with drug-related pustular eruptions
Other skin signs such as facial edema, purpura, target-like
lesions and blisters have been described but are not typical with an acute course, who had no history of psoriasis.
for AGEP. Diagnostic criteria for AGEP were established by Over time, cases with similar clinical characteristics
an international committee of experts, the European Study of have been described using different names, such as
Severe Cutaneous Adverse Reactions (EuroSCAR). The most “generalized toxic pustuloderma”, “blistering drug
relevant histopathological feature is represented by the detec-
eruptions”, and “generalized pustular dermatosis”.1
tion of non-follicular subcorneal and/or intracorneal spongi-
The term acute generalized exanthematous pustulo-
form pustules that are usually large, contiguous and tend to
sis (AGEP) was first introduced by Beylot et al. in
coalesce. After elimination of the causative drug, pustules usu-
ally spontaneously disappear in a few days with desquama- 1980.2, 3 AGEP was better defined later by Roujeau
tion and the reaction fully resolves within 15 days. Internal et al.4 and Chang et al.5
organs are not usually involved and no systemic treatment is In most cases (more than 90%) it arises as an ad-
required. Withdrawal of the culprit drug is mandatory. Al- verse drug reaction even if other rarer toxical and
though AGEP is a self-limiting disease with a favourable prog-
infectious causes have been reported (Table I). The
nosis, secondary infections are a not infrequent complication
incidence of AGEP is estimated at one to five cases
in patients in poor general medical conditions. The reported
per million people per year, even though this figure
mortality is about 5%. The most severe cases are associated
with drug rechallenge. may be underestimated and misdiagnosed as pus-
Key words: Acute generalized exanthematous pustulosis - Pa- tular psoriasis.6, 7 Although AGEP is generally ac-
thology - Diagnosis. cepted as a distinct entity, clinical, etiologic and his-
topathologic features may hardly be distinguished
from drug-induced psoriasis and, to a lesser extent,
Acute generalized exanthematous pustulosis from other pustular widespread neutrophilic derma-
(AGEP) is a rare, acute, febrile eruption, char- tosis.
acterized by the occurrence of numerous small, non-
follicular, sterile pustules, arising within large areas
Materials and methods
Corrisponding author: C. Vassallo, MD, Department of Dermatology,
We conducted a retrospective study of all patients
University of Pavia, Policlinico San Matteo IRCCS Foundation, Viale C.
Golgi 19, 27100 Pavia, Italy. E-mail [email protected] admitted to our department for AGEP between 2008
Vol. 149 - No. 3 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 281
VASSALLO ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS
Table I.—Some of the most frequently involved drugs causing AGEP.
Group Specific Agent
Antibiotics Amoxicillin (with or without clavulanic acid) propicillin, imipenem, cephalexin and cephradine, co-trimoxazole,
doxycycline, chloramphenicol, ciprofloxacin, norfloxacin, ofloxacin, teicoplanin, streptomycin, isoniazid, metro-
nidazole
Antimycotics Terbinafine, fluconazole, itraconazole, nystatin
Anticonvulsant Sertraline, chlorpromazine, nitrazepam
Antihypertensive Diltiazem, captopril, enalapril, furosemide, hydrochlorothiazide
Others Hydroxychloroquine, pyrimethamine, salazopyrine, mesalazine, azathioprine, cytarabine, piperazine ethi-
onamate, pseudoephedrine, allopurinol, dextropropoxyphene, icodextrin, mexiletine, morphine, acetylsalicylic
acid, naproxen, deltaeparin, intravenous non-ionic contrast agents
and 2013 (6-year period): a series of seven patients direct immunofluorescence; a pustular smear was
has been considered. All the patients were rated with made from a recent lesion in order to exclude an in-
the EuroSCAR score and five out of seven were fectious etiology. In all cases the culprit drug was
classified as affected by AGEP. Three male and two suspended and a systemic and/or topical corticoster-
female patients are reported (mean age 66.6). All oidal therapy was started. Resolution of cutaneous
the patients had different comorbidities requiring a lesions with superficial desquamation was observed
therapy with a specific drug that in each case was of in all cases.
recent introduction. In each case reported the patient
presented a rather abrupt occurrence of erythema-
tous patches quickly followed by the appearance of Results
dozens of millimetric non follicular, monomorphous
pustules, associated with a burning sensation and Results are reported and summarized in Table II,
pruritus. In all cases lesions had focal distribution where clinical features, causative drugs, histopatho-
with a tendency to spread rapidly and to coalesce. logical and immunopathological findings are report-
In two patients, a palmar involvement was observed, ed for each patient. Microbiological examinations
while in one woman mucosal (oral) involvement from pustular smears always proved negative. In all
was evident. Admission to our in-patient department cases direct immunofluorescence was negative and
was required in two cases. Patients were all inves- histopathological examination (Table III) was al-
tigated for laboratory findings, including full blood ways consistent with a diagnosis of AGEP present-
count, creatinine, transaminases, bilirubin, gamma- ing with subcorneal and intracorneal pustules with
glutamyl peptidase and inflammatory markers. In only scant spongiosis and few necrotic keratinocytes.
each case two punch biopsies were performed, re- Rare eosinophils in superficial dermis were evident
spectively for histopathological examination and in three patients.
Table II.—Main clinical features of five patients affected by AGEP.
Patient
Mucosal
gender Main comorbidities Causative drug Cutaneous involvement Systemic involvement
involvement
age
1 (CR), F Rheumatoid arthritis Hydroxychloroquine Trunk, arms, legs, face Lips Fever, 38 °C, leukocytosis
70 yrs-o with neutrophilia, elevation of
inflammatory markers (hospitalized)
2 (CG), M Dermatomyositis Hydroxychloroquine Arms, legs, palms // Leukocytosis with neutrophilia,
76 yrs-o elevation of inflammatory markers
3 (DL), M Hairy cell leukaemia Pentostatin Neck, trunk, legs // Fever; rhabdomyolysis (hospitalized)
60 yrs-o
4 (CG), F Diabetes mellitus Naproxen sodium Trunk, palms // Leukocytosis with eosinophilia, slight
68 yrs-o arthrosis elevation of inflammatory markers
5 (GF), M Hypertension Amoxicillin + clavu- Face, trunk (folds) // Slight elevation of inflammatory
59 yrs-o lanic acid markers
282 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA June 2014
ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS VASSALLO
Table III.—Histopathological findings in five patients affected by AGEP.
Immunopathological
Patient Histopathological features: epidermal changes Histopathological features: dermal changes
features
1 DIF negative Basket-wave corneum, scant sub/intraepidermal Slight edema of papillary dermis, scant interstitial
non spongiform pustules, spongiosis, neutrophilic inflammatory infiltrate composed of lymphocytes,
exocytosis neutrophils, and few eosinophils
2 DIF negative Subcorneal pustules, focal spongiosis, neutrophils at Edema of sub-papillary dermis, extravasation of
dermo-epidermal junction erythrocytes, interstitial infiltrate of neutrophils
and lymphocytes, no eosinophils
3 DIF negative Parakeratosis, focal scale-crust, subcorneal pustules, Slight edema of papillary dermis, scant inflam-
spongiosis, rare single necrotic keratinocytes matory infiltrate composed of lymphocytes,
neutrophils and many eosinophils. Erythrocytes
extravasation
4 DIF negative Subcorneal pustules, scant focal spongiosis, neutro- Edema of sub-papillary dermis, erythrocytes
phils exocytosis, rare single necrotic keratinocytes extravasation, interstitial infiltrate of neutrophils
and lymphocytes, few eosinophils
5 DIF negative Confluent subcorneal pustules, slight spongiosis, Scarce infiltrate of lymphocytes and neutrophils
neutrophils along the dermo-epidermal junction in an oedematous superficial dermis. No eosino-
phils
Clinicopathologic correlations in the five AGEP pa‑ was necessary. Laboratory findings showed leuco-
tients considered cytosis with neutrophilia and elevation of inflamma-
tory markers. No other internal organ involvement
Case 1 was documented. A pustular smear from a new le-
sion was performed and allowed us to exclude an
A 70-year-old woman, affected by rheumatoid ar-
infectious cause of lesion. Two punch biopsies were
thritis developed erythematous and edematous patch-
performed, on for direct immunofluorescence (nega-
es, quickly covered by pustular lesions. She was in tive) and one for histopathologic examination, con-
treatment with hydroxychloroquine for one month firming the clinical diagnosis of AGEP. In particular
before cutaneous eruption. These manifestations be- basket-wave corneum, scant sub/intraepidermal non
gan on the trunk and rapidly spread to legs, arms, spongiform pustules, spongiosis, neutrophilic exo-
face and oral mucous membranes (lips) (Figure 1). cytosis were observed. The dermis was characterised
These widespread cutaneous lesions were associated by slight oedema of papillary dermis, scant intersti-
with fever (38 °C), pruritus and burning sensation tial superficial inflammatory infiltrate composed of
and altered blood clotting analysis. Hospitalization lymphocytes, neutrophils, and few eosinophils.
Case 2
A 76-year-old man affected by dermatomyositis in
therapy with systemic corticosteroids started also a
therapy with hydroxychloroquine, developing with-
in some days erythematous and edematous patches
with small, monomorphous pustular lesions all over
the body surface (Figure 2) with even a palmar in-
volvement. No mucosal localization was present and
good clinical general conditions were documented.
Only leukocytosis with neutrophilia and slight el-
evation of inflammatory markers were detectable.
A pustular smear was performed from a recent le-
sion and resulted negative for micro-organisms.
Two punch biopsies were taken: the first one for
Figure 1.—AGEP: mucous membrane involvement. Mucosal
DIF proved negative and the other one was consist-
localization is reported in only one third of cases, being almost
exclusively oral. Pustular lesions evolve into superficial erosions. ent with a diagnosis of AGEP. The histopathologic
Vol. 149 - No. 3 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA 283
VASSALLO ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS
Figure 3.—Subcorneal pustule filled by several neutrophils (he-
matoxylin-eosin).
Figure 2.—AGEP: early stage. Presence of erythematous and
oedematous patches on the neck and on the trunk. Lesions were
associated with hitch. Within a few hours the occurrence of sev-
eral, monomorphous, millimetric pustules could be documented. Figure 4.—Neutrophils along dermal-epidermal junction (hema-
toxylin-eosin).
features presented with subcorneal pustules (Figure to trunk, neck and legs. Mucous membrane was not
3), focal spongiosis, neutrophils at dermo-epidermal involved. A systemic involvement was documented
junction (Figure 4), edema of sub-papillary dermis, by the presence of fever (>38 °C), elevation of in-
extravasation of erythrocytes, interstitial infiltrate of flammatory markers and rhabdomyolysis, that could
neutrophils and lymphocytes, no eosinophils. be interpreted as due to chemotherapy. The patient
was admitted to our in-patient department. Pustular
smear was performed and resulted negative as well as
Case 3
direct immunofluorescence. Histopathology showed
A 60-year-old man affected by hairy cell leukemia parakeratosis, focal crusty lesions, subcorneal pus-
started chemotherapy with granulocyte colony stim- tules, spongiosis, rare single necrotic keratinocytes,
ulating factors (GCSF) and pentostatin. About 15 slight oedema of papillary dermis, extravasation of
days later he developed erythematous patches cov- erythrocytes scant inflammatory infiltrate composed
ered by small, monomorphous pustules, localized of lymphocytes, neutrophils and many eosinophils.
284 GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA June 2014