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Médico cirujano
Chromomycosis
Description
A 55-year-old woman living in a rural area of Oaxaca, southeast Mexico, presented with an
11-year history of 2 warty-like erythaematous and painful plaques, 10–12 cm long on her
right leg (figure 1). There was no evidence of any underlying disease. Skin biopsy revealed
pseudoepitheliomatous hyperplasia with fumagoid cells. Tissue culture grew a black fungus
with a velvety texture, later identified as Fonsecaea pedrosoi, on microscopic examination
(figure 2). Oral itraconazole 200 mg twice daily was initiated.
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
CROMOMICOSIS
En la zona rural de Oaxaca una mujer de 55 años presentaba dos placas eritematosas y dolorosas,
más establecido como una placa verrugosa eritematosa con superficie áspera y escamosa, con
centro atrófico y bordes bien delineados muy parecidas a verrugas durante 11 años, en la imagines
se puede observar esta lesión en su pierna derecha.
En su tobillo derecho igualmente contenía una placa con superficie áspera y escamosa con costras
milimétricas de color marrón.
La cromoblastomicosis es una micosis subcutánea crónica causada con frecuencia por hongos
dematiáceos, F. pedrosoi, con distribución mundial, especialmente en áreas tropicales como
Madagascar, Brasil, Costa Rica, República Dominicana y México, incluido Oaxaca.
Afecta principalmente a los hombres de los cuales son inmunocompetentes y se relaciona con
actividades ocupacionales, por inaculacion traumatica principalmente en las piernas.
Se recomiendan altas dosis de itraconazol (400 mg / día) o terbinafina (500 mg / día), aunque las
tasas de recurrencia son altas en la enfermedad de larga duración y extensa.
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
Coccidioidomycosis
Introduction
The dimorphic fungus coccidioides causes coccidioidomycosis, also known as San Joaquin
Valley fever, which is endemic to the arid regions of the Western
Hemisphere. Coccidioides was first discovered by a medical intern in 1892 and was later
named Coccidioides immitis. Coccidioidomycosis is the second most common fungal
infection in the United States, and it has a wide spectrum of clinical manifestations, from
asymptomatic infection to fatal disease.
Etiology
Coccidioides is a genus of dimorphic fungi that exist as mycelia or as spherules (1). Both
mycelia and spherules are asexual forms. The sexual form of coccidiosis has not been
found. Molecular analysis suggests Coccidioides is related to ascomycetes such
as Histoplasma capsulated or Blastomyces dermatitidis. Two species within the genus
coccidioides are recognized namely, C. immitis and Coccidioides posadasii. C. immitis is
found in California while C. posadasii is found in other US states as well as other parts of
the world. The clinical manifestation and in vitro susceptibilities of these two species are
the same. The two species of coccidioides are phenotypically identical and can only be
identified by molecular methods. Therefore, Coccidioides species are not routinely
identified to species level in clinical microbiology laboratories. This fungus likes arid
desert with high salt content. In soil, and in agar, the Coccidioides grow as mycelia or
filamentous form.
Arthroconidia, the infectious particles of Coccidiosis species are deposited in the lung when
inhaled. Arthroconidia transform to spherules in the lung and tissues. Spherules are filled
with endospores (2 micrometers to 5 micrometers). This spherule can burst in tissues
releasing endospores, which can magnify the infection.
Coccidioides species grow well on most mycologic or bacteriologic media after five or
seven days of incubation. Typically, the colonies are white. However, appearance is
nondiagnostic. The yeast is very infectious at this stage. Outbreaks in the laboratory
personnel have occurred; therefore, the laboratory must be informed
when Coccidiosisspecies are suspected.
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
Epidemiology
Coccidioides is endemic to California, Arizona, Utah, Nevada, and New Mexico.
Coccidioidomycosis is a reportable disease. For unknown reasons, the incidence rates in
Arizona have increased lately. In 2011, the incidence of coccidioidomycosis was 42.6 cases
per 100,000 population and highest among persons aged 60 to 79 years (69.1/100,000). In
some areas within the endemic region, Valley fever can cause an estimated 15% to nearly
30% of community-acquired cases of pneumonia. C. immitis can cause disease in non-
endemic regions due to wind carrying the infectious particles over long distances.
Pathophysiology
Coccidioides species exist as mycelia in the environment and the laboratory. Mycelia grow
by apical extension forming true septae along their course. In one week, these mycelial
cells undergo a process of autolysis and thinning of their cell walls. Some of the remaining
cells in the colony are transformed into barrel-shaped, loosely adherent arthroconidia. The
arthroconidia are loosely connected to each other, becoming airborne at the slightest
perturbation. Arthroconidia are 2 microns to 5 microns in length and are of the right size to
reach the terminal bronchiole when inhaled. Once inside the lung, arthroconidia undergo
remodeling from rectangular to spherical forms known as spherules. This transformation is
facilitated by the shedding of the outer layer of the arthroconidia.
The spherules grow to the size of 75 microns in diameter. The spherules divide internally
by developing internal septae, which divide the spherule into compartments. Each
compartment has endospores. As spherule impregnated with endospores grows, it
eventually ruptures and releases the endospores in the region including the alveolar sacs.
These endospores are picked up by the alveolar macrophages. The local release of
endospores causes host response, and acute inflammation ensues. The endospores are
capable of further multiplication within tissues and when released in the environment can
lead to mycelial growth.
Occasionally, in susceptible patients, spherule may leave the lung to set up
an extrapulmonary infection. The most likely routes of dissemination appear to be due to
trafficking of the macrophages carrying the spherules or the endospores. Mediastinal
lymphadenopathy is frequently seen in coccidioidomycosis patients who have
an extrapulmonary disease.
Histopathology of the tissues infected with coccidioidomycosis shows cellular components
of both acute and chronic inflammation. Neutrophils and eosinophils are attracted to the
local region when spherules rupture and release endospores. Chronic granulomatous
infection is associated with mature unruptured spherules suggesting that the infection due to
Ccoccidioides species has been controlled.
The mainstay of the defense against Coccidioides species are the T-
lymphocytes, particularly the T-helper2 lymphocytes (Th2). Th2 dysfunction or deficiency
has been found in patients with an extrapulmonary or disseminated disease. The innate
cellular immunity is useful in the early infection when the arthroconidia reach the terminal
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bronchioles, when spherules are small, or when the endospores are released. As the
spherules grow larger, the effector cells of innate immunity, for example, neutrophils,
monocytes, and natural killer cells become ineffective.
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
Evaluation
Isolating Coccidioides organisms in a patient is definite evidence of a coccidioidal
infection, and this diagnostic approach is used most frequently in patients with complicated
pulmonary or disseminated syndromes. Sputum collection has no risk of transmission.
Professionals most frequently use serologic testing to diagnose primary coccidial
infections. Often, the patients may not have sputum production, and fungal cultures are not
feasible. CSF cultures are often negative in coccidioidomycosis. Minimally reactive test
results should not be dismissed as insignificant. A negative serologic test result does not
exclude the presence of a coccidial infection. Therefore the test should be repeated over the
course of two months.
Detection of tube precipitin antibodies is sometimes called IgM test. The polysaccharide
antigen of the fungal cell wall is responsible for this antibody. Tube precipitin antibodies
are detected in 90% of patients in first three weeks after exposure. The prevalence of tube
precipitin antibodies decreases to 5% by seven months after exposure. Complement-fixing
antibodies (CF) are immunoglobulin G (IgG), and the antigen responsible for these
antibodies is chitinase. Complement-fixing antibodies can be detected in other body fluids,
and their detection in cerebrospinal fluid is an especially important aid to the diagnosis of
coccidial meningitis. Complement-fixing antibody concentration is expressed as a titer,
such as 1:4 or 1:64.
An enzyme immunoassay (EIA) to detect Coccidiosis IgM and IgG antibodies are
available. However, the results are not interchangeable with the immunodiffusion (ID) and
CF tests because different antigens are used for EIA. Enzyme immunoassay results should
be confirmed with immunodiffusion tube precipitin, immunodiffusion complement-fixing
(IDCF), or complement-fixing test (CF) because these tests have established a track record.
Nevertheless, positive results with the EIA commercial kit are highly sensitive (95%) for
coccidiosis infection, but false-positive results occur more frequently when compared to TP
and CF tests.
Antibodies detected by the original tube precipitin or complement-fixing tests can be
detected by alternative procedures known as the immunodiffusion tube precipitin and
immunodiffusion complement-fixing tests. Although these tests are conducted similarly,
different antigens are used to measure different types of antibodies. Test results are as
sensitive as the tube precipitin and compliment fixing antibody detection tests.
Overall, the serological tests are likely to be positive in a normal host who has been
exposed to Coccidioides species. In a study of 41 patients with culture-confirmed
coccidioidomycosis, the CF was positive in 23 (56%), the IDCF in 29 (71%), and the EIA
in 34 (81%). In six (15%) patients, all serologic tests were negative.
Polymerase chain reaction (PCR) probes to detect coccidiosis DNA directly in patient’s
clinical specimens are not available commercially. Genomic studies in research settings
show that PCR tests are 98% sensitive and 100% specific.
A specific ribosomal RNA sequence can be detected using a commercially available DNA
probe (Gen-Probe, San Diego) in mycelia grown in the laboratory. At present, molecular
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
methods to differentiate between C. immitis and C. posadasii are available only at a limited
number of reference laboratories.
Latex tests are simple to use and are widely available in clinical settings but are less
sensitive. There are significant numbers of false positive reaction.
Antigenemia and antigenuria may occur with early or chronic coccidioides infections. The
PCR test, if applied to CSF, is particularly useful for diagnosis of meningitis because
frequently the CSF cultures are negative. In a study of 24 immunosuppressed patients with
coccidioidomycosis, most (17/24; 71%) had a positive test for antigen in the urine. The
Histoplasma antigenuria assay was positive in 14 of these patients, confirming the cross
reactivity between the two fungi.
Treatment / Management
In 2016, the Infectious Disease Society of America published treatment guidelines for
coccidioidomycosis. Coccidioidomycosis has a wide clinical spectrum of presentation.
Patients can have a mild respiratory illness with infiltrates or can have chronic pulmonary
disease presenting as nodules, cavities, or fibrocavitary disease. In a small percentage of
mostly immunocompromised patients, the coccidioidomycosis can present as disseminated
disease. The preferred drug is Diflucan in a dose of 400 mg to 1200 mg daily. Itraconazole
is an alternative, but there are increased drug interactions with itraconazole.
Pulmonary Infections
Primary pulmonary infections, if severe, should be treated. Some of the reasons to treat a
patient are as follows:
weight loss of 10% or more
intense night sweats persisting symptoms longer than three weeks
infiltrates involving more than one-half of one lung or bilateral lung involvement
prominent hilar adenopathy
CF antibody test titers of equal to or greater than 1:16
inability to work due to symptoms
symptoms persist for 12 months
patient age greater than 55 years.
Three months treatment with oral azole should suffice.
Asymptomatic pulmonary nodules due to coccidiosis infection should be followed by
imaging. If the nodule is growing, and if there is a concern for malignancy, then resection
of the nodule should be considered. Post-resection, there is no need to treat unless the
patient is immunocompromised. Some experts would treat for three months as mop up
therapy, if there were live yeasts present in the pathology specimen (unpublished data).
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Asymptomatic cavities should be followed with serial imaging. If the cavity persists for
over two years, is close to the pleura, or is enlarging, some experts recommend resection to
avoid future complications, although good evidence is lacking. Cavitary
coccidioidomycosis can be treated if there is local discomfort, superinfection with other
fungi, or bacteria, if there is hemoptysis or rupture of the cavity into the pleural space with
resulting pyopneumothorax. Treatment durations are about three to six months.
Treatment with azoles, such as fluconazole, is recommended for patients with fibrocavitary
disease. If there is sufficient response, these patients should be treated for a year. Surgical
management may be needed for severe localized disease, particularly if hemoptysis has
occurred.
In patients who have diffuse pneumonia, such as with bilateral diffuse reticulonodular or
miliary infiltrates, Amphotericin B may be used. These patients have had exposure to a
large inoculum, or there could be an underlying unrecognized immunocompromised state.
Patients with diffuse pneumonia should also be evaluated for extra pulmonary coccidiosis
infection.
Coccidioides Meningitis
Coccidioides meningitis does not respond to intravenous (IV) Amphotericin due to poor
bioavailability across the blood brain barrier (BBB). It can present in a variety of ways, but
the most common symptom is a headache. Hydrocephalus is common and may be present
early or late during the disease and is a common complication. The most common life-
threatening complication of coccidial meningitis in the modern era is CNS vasculitis
leading to cerebral ischemia, infarction, and hemorrhage. Clinically, a patient may present
with cerebral infarction and stroke. Spinal arachnoiditis (SA) may occur as a complication,
but unlike infarctions and hydrocephalus, arachnoiditis is not an initial presentation.
Recently, there has been an increase in the incidence of spinal arachnoiditis post treatment
with azole antifungal agents. SA responds better to intrathecal amphotericin B. Cerebral
abscesses and mass lesions secondary to Coccidioides infection have rarely been reported.
Eosinophils in CSF are uncommon, but when present, are suggestive of the diagnosis. More
typical is the lymphocytic predominance but often neutrophil predominance is seen.
Fluconazole was demonstrated to be equivalent to amphotericin B in 1988 and since then
has been the drug of choice at 800 mg to 1200 mg daily dose. Both clinical and CSF
parameters should be monitored at least monthly. Once improvement occurs, follow up
may be done every three months for life. Therapy is lifelong in these patients.
HIV Patients
The infection rate has declined dramatically since the advent of antiretroviral therapy
(ART). The pulmonary disease is often diffuse and can be confused with Pneumocystis
jiroveci pneumonia. During the peak of the epidemic, about half of the patients with
coccidiosis infection were outside of endemic areas. Therefore, coccidioidomycosis in HIV
patients should be in the differential regardless of the location. The symptoms of meningitis
in HIV patients are identical to those of non-HIV patients. A headache is frequently
present.
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
All HIV patients with clinically active coccidioidomycosis must be treated if CD4 counts
are below 250. Patients on ART, whose CD4 counts are over 250 and stable, can safely
stop therapy. Patients who had meningitis should continue therapy indefinitely. All
localized pulmonary infections should be treated in HIV patients. While oral azole can be
used for a mild infection, amphotericin B is preferable for moderate to severe infections.
Combination therapy with azole and amphotericin B is recommended in severe infections.
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
coccidioidomycosis
El hongo dimorfo coccidioides causa coccidioidomicosis, también es conocida como fiebre del
Valle de San Joaquín y predomina en las regiones áridas del hemisferio occidental.
Esta enfermedad es la segunda infección más común en EEUU y contiene un amplio espectro
clínico que va desde lo asintomático hasta una enfermedad mortal.
Se reconocen dos especies dentro del género coccidioides, a saber, C. immitis y Coccidioides
posadasii. C. immitis se encuentra en California, mientras que C. posadasii se encuentra en otros
estados de EE. UU. Y en otras partes del mundo.
Este hongo le gusta el desierto árido con alto contenido de sal. En el suelo y en agar, los
Coccidioides crecen como micelios o forma filamentosa.
La esferulas se llenan de endosporas (de 2-5 micrómetros) que al estallar libera esporas
aumentando así la infección.
Colonias blancas con 5 a 7 días de incubación la cual es altamente infecciosa en esta etapa.
En 2011, la incidencia de coccidioidomicosis fue de 42,6 casos por 100.000 habitantes y la más alta
entre las personas de 60 a 79 años (69,1 / 100.000).
En algunas áreas dentro de la región endémica, la fiebre del valle puede causar un estimado del
15% a casi el 30% de los casos de neumonía adquiridos en la comunidad.
Existen como micelos en el ambiente y crecen por extensión apical formando septos. En una
semana se someten a autolisis y adelgazamiento de pared celular y las restantes se forman
Artroconifdios que tienen forma de barril y poco adherentes los cuales tienen el diámetro
adecuando para llegar al broquiolo terminal.
Las esférulas se dividen internamente mediante el desarrollo de septos internos, que dividen la
esférula en compartimentos. Cada compartimento tiene endosporas. A medida que crece la
esférula impregnada con endosporas, finalmente se rompe y libera las endosporas en la región.
Estas endosporas son recogidas por los macrófagos alveolares. La liberación local de endosporas
causa la respuesta del huésped y se produce una inflamación aguda. Las endosporas son capaces
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
de una mayor multiplicación dentro de los tejidos y cuando se liberan en el ambiente pueden
conducir al crecimiento micelial.
Pueden llegar a diseminarse de manera extra pulmonar debido al tráfico de macrófagos que llevan
las esferulas o endoesporas.
Es característico presentar una inflamación aguda y crónica, los neutrófilos y los eosinófilos son
atraídos por la región local cuando las esférulas se rompen y liberan endosporas. La infección
granulomatosa crónica se asocia con esférulas maduras no rotas que sugieren que la infección
causada por la especie Ccoccidioides ha sido controlada.
EL pilar de línea de defensa son los linfocitos T, particularmente los linfocitos T-helper2 (Th2), la
disfunción o deficiencia de Th2 se ha encontrado en pacientes con una enfermedad extrapulmonar
o diseminada.
Un 60% de los casos son asintomáticos y al presentarse lo síntomas se confunde con neumonía
bactreriana.
Los síntomas aparecen de siete a 21 días después de la exposición. Fiebre, tos, dificultad para
respirar (SOB) y dolor en el pecho son los más frecuentes. La presentación clínica puede ser aguda
o subaguda en función del tamaño del inóculo. A menudo se observa dolor de cabeza, pérdida de
peso y erupción. La erupción es débil, maculopapular, transitoria, y ocurre temprano durante la
enfermedad y, por lo tanto, a menudo se pasa por alto. El eritema nodoso o el eritema multiforme
ocurre con mayor frecuencia en las mujeres. Las artralgias migratorias también son comunes. La
tríada de fiebre, eritema nodoso y artralgias (especialmente de rodillas y tobillos) se ha
denominado reumatismo en el desierto. Los hallazgos de laboratorio incluyen la tasa de
sedimentación globular elevada (VSG) y la eosinofilia. La radiografía de tórax (CXR) muestra
infiltrados unilaterales. La adenopatía hiliar y peritraqueal sugiere la diseminación extratorácica de
la enfermedad. Las cavidades pulmonares están presentes en solo el 8% de los adultos, pero son
más frecuentes en los niños.
Se utilizan lruebas serológicas para diagnosticar infecciones coccidiales primarias. A menudo, los
pacientes pueden no tener producción de esputo, y los cultivos de hongos no son factibles. Los
cultivos de LCR suelen ser negativos en la coccidioidomicosis.
Infecciones pulmonares
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Castillo Rodríguez Eder Octavio 5to semestre Lic. Médico cirujano
Las infecciones pulmonares primarias, si son graves, deben tratarse. Algunas de las razones para
tratar a un paciente son las siguientes:
El tratamiento con azoles, como fluconazol, se recomienda para pacientes con enfermedad
fibrocavitaria. Si hay suficiente respuesta, estos pacientes deben recibir tratamiento durante un
año. El tratamiento quirúrgico puede ser necesario para la enfermedad localizada grave,
especialmente si se ha producido hemoptisis.
En pacientes con neumonía difusa, como con infiltrados reticulonodulares o miliares difusos
bilaterales, se puede usar anfotericina B. Estos pacientes han tenido exposición a un inóculo
grande, o podría haber un estado inmunocomprometido subyacente no reconocido. Los pacientes
con neumonía difusa también deben ser evaluados para la infección de coccidiosis pulmonar
adicional.
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