Full text of DOI:10.1016/S0301-0546(02)79135-0

O RIGIN AL ARTICLES
Atopic dermatitis with mononuclear phagocytic
activity deficiency
W.C.N. Forte, M.C. Santos de Menezes, S.M. Cipolli Guerra de Oliveira,
and S. Bruno
Immunology Section of Santa Casa Medical School and Hospital. São Paulo. Brazil.
response of atopic dermatitis patients; the type, de-
gree and prevalence of these defects however are as
yet unclear (5).
SUMMARY
Five patients with atopic dermatitis, three males and
two females, aged 2 to 17 years, had positive reac-
tions to air allergens (Dermatophagoides pteronyssi-
nus and/or farinae). All the patients suffered from se-
vere recurrent dermatophytosis that responded
poorly to antifungal treatment. The results of immu-
nologic evaluation by laboratory tests were normal,
except for a decrease in the ingestion phase by mo-
nonuclear phagocytes.
After diagnosis of immunodeficiency, ketoconazo-
le shampoo was used prophylactically and at the very
first signs of recurrence of dermatophytosis, syste-
mic antifungal treatment was started, without con-
current use of macrolides and with monitoring of he-
patic function. The fungal infections responded well
to this treatment and the patients’ quality of life mar-
kedly improved.
The diagnosis of deficient phagocytic activity by
mononuclear phagocytes is less often made as
compared with the diagnosis of deficient polymorp-
honuclear neutrophil phagocytosis, as seen in chro-
nic granulomatous disease, in malnutrition and ot-
her nutritional disturbances (6-8). In the presence
of altered mononuclear phagocytic activity, serious
infections are encountered especially by fungi, but
also by viruses and intracellular bacteria. Infections
are caused by Candida sp, M. gypseum, T. tonsu-
rans, Mycobacterium tuberculosis and any type of
virus.
The prognosis of atopic dermatitis with immunolo-
gic involvement is directly related to early diagnosis
and specific treatment, as seen in practically all im-
mune deficiencies.
Few cases have been described in the literature of
patients with atopic dermatitis who had deficient mo-
nonuclear phagocytic activity, even though this is so
important for adequate treatment and evolution of
the patients’ disease.
Key w ords: Atopic dermatitis. Dermatophytosis.
Phagocytic deficiency. Monocytes.
INTRODUCTION
CASE REPORTS
First case
Atopic dermatitis or atopic eczema is a chronic and
recurrent inflammatory disease with exacerbations
triggered by different stimuli (1). Clinically, it is cha-
racterized by pruritic lesions with scaling leading to li-
chenification, the latter considered to be the cutane-
ous component of the atopic complex (2, 3).
Several atopic dermatitis patients present recu-
rrent or persistent infections and should be submit-
ted to immunologic evaluation (4). Studies have de-
monstrated some deficiencies in the immunologic
G.P.M., female, 17 years old. At the age of eleven,
she started to present intense pruritis over the who-
le body when the diagnosis of atopic dermatitis was
made. At 13, there was aggravation of the lesions
with diagnosis of Tinea corporis. This was so serious
that she often could not go to school. At the age of
17, she presented papulo-vesicular lesions with eryt-
Allergol et Immunopathol 2002;30(5):263-6

W.C.N. Forte, M.C. Santos de Menezes, S.M. Cipolli Guerra de Oliveira, S. Bruno.— ATOPIC DERMATITIS
WITH MONONUCLEAR PHAGOCYTIC ACTIVITY DEFICIENCY
264
hematous base and serous exudate associated with
whitish round lesions with definite contour, dissemi-
nated all over her body, in which state she was first
seen at our Immunology Section. There was also an
intense vaginal discharge.
Fifth case
J.A.S., female, 17 years old. At the age of two,
she had erythematous exudative lesions on the face.
At the age of three, these lesions spread to the who-
le body, except hand palms and foot soles, with in-
tense pruritis. At the age of seven, there was aggra-
vation of her condition, when she arrived at the
Immunology Section with severe atopic dermatitis
with fungal infection.
Second case
T.A.S., male, 2 years old. Diagnosis of atopic der-
matitis was made at the age of one. The clinical pre-
sentation aggravated when the atopic dermatitis de-
veloped fungal infection which responded poorly to
topical treatment as well as frequent recurrences.
At the age of 2, he was brought to the Immunology
Section with intense pruritis, papulo-vesiculo-erythe-
matous confluent lesions predominantly on the face,
extensor regions and lower members associated
with crusty lesions.
RESULTS
Our patients were positive for air allergens
(Dermatophagoides pteronyssinus and/or farinae).
Cultures of skin scales showed Candida sp, M. gyp-
seum and dermatophyte T. tonsurans. In the first
case, Candida sp was found in the vaginal discharge.
In all five patients, the values of immunoglobulins,
lymphocytes, T and B cells, CD4 + and CD8 + cells,
C3 and C4 components of complement as well as
chemotactic and phagocytic activity for neutrophils
were normal while phagocytosis was persistently de-
creased in monocytes.
Third case
F.C.N., male, 12 years old. Diagnosis of atopic der-
matitis was made at the age of three. At the age of
four, he developed Cryptococcus neoformans me-
ningitis confirmed by positive cerebrospinal fluid cul-
ture, associated with whitish oral mucosa lesions.
At the age of ten, he developed crusty erythematous
lesions on the face, trunk and members.
All five patients showed decreased phagocytic in-
gestion phase for monocytes (table I) when compa-
red to normal values: 27 ± 9; 78 ± 7; 75 ± 10 to
27 ± 5; 65 ± 7; 68 ± 7, according to age (9).
After the diagnosis of atopic dermatitis with der-
matophytosis, associated with deficient monocyte
phagocytic activity was made, all patients received
systemic antifungal treatment during the fungal in-
fection. No concurrent macrolides were given and
there was control of hepatic transaminases and coa-
gulation tests. Prophylactic use of cetoconazol sham-
poo was also initiated. Immediately at first signs of
fungal infection, systemic antifungal therapy was
started once more, always with hepatic function con-
trol. The patients started to have satisfactory respon-
se to the treatment.
Fourth case
H.G.M., female, 12 years old. At the age of three,
she presented with disseminated maculo-papular le-
sions, mainly on the extensor surface of the mem-
bers, which progressed to lichenification. There was
aggravation and at the age of four, there was alopecia
with tonsured hair, areas of scaling on the face,
trunk, upper members, nail thickening, labial fissu-
res and repeated viral infections.
DISCUSSION
Table I
Results of chem otaxis and phagocytosis evaluation
of m onocytes
Zimosan (Zy) particle phagocytosis used in our
methodology assesses the monocyte ingestion pha-
se (9). Monocytes present receptors for C3b and C5b
implicated in the ingestion phase of phagocytosis,
where C5b is considered the more important one.
Mononuclear cell incubation with serum promotes
complement activation, resulting in the formation of
C3b and C5b components which unite to Zimosan
particles. The union of C3b and C5b with their res-
pective receptors on the surface of monocytes cul-
Chemotaxis (micra) Phagocytosis (% )
Case
Case
Monocytes
1.º 2.º 3.º 4.º 5.º 1.º 2.º 3.º 4.º 5.º
Control
28 18 23 29 41 09 19 21 15 1 8
36 35 42 81 66 35 32 47 62 30
36 35 46 83 69 35 37 52 68 41
With homologous serum
With autologous serum
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W.C.N. Forte, M.C. Santos de Menezes, S.M. Cipolli Guerra de Oliveira, S. Bruno.— ATOPIC DERMATITIS
WITH MONONUCLEAR PHAGOCYTIC ACTIVITY DEFICIENCY
265
minates with the ingestion of the Zimosan particles
by these phagocytes. The control test evaluates the
viability of the method with spontaneous particle in-
gestion. The second and third tests evaluate zimosan
ingestion in the presence of C3b and C5b compo-
nents of heterologous and homologous serum res-
pectively.
tern in the immune response of atopic dermatitis, but
results have been conflicting, while the main studies
realized have used stimulation by different mitogens,
which makes comparison difficult (20). Fisher et al
have observed significant decrease in chemotaxis
by monocytes in patients with serious mucocutane-
ous candidiasis and also in some patients with ato-
pic dermatitis (21).
The results demonstrated no significant difference
between the second (mononuclear leucocytes incu-
bated with Zy and human serum “pool”) and the third
test (mononuclear leucocytes incubated with Zy and
the patient’s serum), with normal complement values
of these patients (10), indicating that the decrease in
phagocytosis was due to an intrinsic monocytic de-
fect. These data are coherent with the greater fre-
quency of fungal infections in these patients. The chil-
dren studied were of normal height and weight,
which makes it impossible that the phagocytic defi-
ciency in monocytes might be due to malnutrition (9).
Studies confirm that the skin of atopic dermatitis
patients is more frequently colonized by
Staphylococcus aureus than non-atopic individuals
and that this colonization is more intense in the pre-
sence of more serious degrees of dermatitis, which
contributes to the chronicity of the disease (11, 12).
Patients with atopic dermatitis may show exacer-
bation of their eczema which is triggered by various
inflammatory stimuli, through IgE mediated mecha-
nism, including to dermatophytes; these patients
thus become sensitized to these agents and are
more susceptible to cutaneous dermatophyte infec-
tions (1, 13). The positive tricofitin reactivity observed
in atopic dermatitis does not necessarily signify sen-
sibilization to the dermatophytes but is probably a
sign of cross-reaction to fungus (14).
Candida albicans which belongs to the normal hu-
man microflora, can induce synthesis of specific IgE
in patients with atopic dermatitis and asthma. The
Candida albicans sensibilization manifested in chil-
dren with serious atopic dermatitis is frequently as-
sociated with immunodeficiency (15) and has been
suggested as a component of the atopic dermatitis
pathogenesis (16). On the other hand, eczema is one
of the cutaneous manifestations of primary immuno-
deficiency which leaves a doubt as to the initial dise-
ase factor (17). Neutropenic patients have greater
risk to develop systemic infections by Candida albi-
cans, while the fungus also has the ability to activate
Th2 response as evasive strategy (18, 19).
These observations as well as the literature propo-
se the hypothesis of deficient mononuclear leukocy-
te phagocytic activity in patients with atopic dermati-
tis associated with fungal infections and alert that
special therapeutic measures must be taken in order
to improve these patients’ quality of life.
RESUMEN
Cinco pacientes con dermatitis atópica, tres varo-
nes y dos mujeres, de 2 a 17 años de edad, tuvieron
reacciones
positivas
a
neuroalergenos
(Dermatophagoides pteronyssinus o farinae). Todos
padecían una dermatofitosis grave y recurrente que
respondían con dificultad al tratamiento antifúngico.
La evaluación inmunológica mediante pruebas analí-
ticas fue normal, excepto por la presencia de dismi-
nución de la fase de ingestión por fagocitos mono-
nucleares.
Después de diagnosticar la inmunodeficiencia, se
utilizó de manera profiláctica champú de ketocona-
zol y ante los primeros signos de recidiva de la der-
matofitosis se inició tratamiento antifúngico por vía
general, siempre sin el uso concurrente de macróli-
dos y con control de la función hepática. Las infec-
ciones fúngicas ahora respondieron bien y la calidad
de vida de los pacientes mejoró considerablemente.
Palabras clave: Dermatitis atópica. Dermatofitosis.
Deficiencia fagocítica. Monocitos.
Correspondence:
Dra. Wilma Carvalho Neves Forte
Alameda Barros,399. Apto162. Higienópolis
São Paulo/SP Brasil
CEP 01232-001 TEL. 55-11-99964800
TEL. 55-11-3666-7150
An increasing number of children with atopic der-
matitis are recognized to possess immune defects,
while the exact incidence is still unknown (5).
Monocytes and T helper lymphocytes exert an im-
portant role in the immunologic dysfunction of ato-
pic dermatitis. Studies have evaluated the citocin pat-
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W.C.N. Forte, M.C. Santos de Menezes, S.M. Cipolli Guerra de Oliveira, S. Bruno.— ATOPIC DERMATITIS
WITH MONONUCLEAR PHAGOCYTIC ACTIVITY DEFICIENCY
266
12. Bratton DL, May KR, Kailey JM, Doherty DE, Leung DY.
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