acute systemic histoplasmosis associated with chorioretinitis in an.docx
TRANSCRIPT
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
1/17
HISTOPLASMOSIS AKUT SISTEMIK TERKAIT DENGAN
CHORIORETINITIS PADA REMAJA IMUNOCOMPETENT
Abstrak
Histoplasmosis adalah penyakit endemik, mikosis sistemik yang disebabkan oleh jamur dimorfik
HistoplasmaCapsulatum. Sebuah minoritas pasien menderita asimtomatik chorioretinitis yang
dikenal sebagai Presumed Ocular Histoplasmosis Syndrome (POHS), yang biasanya dikaitkan
dengan jaringan parut dan atrofi peripapillary chorioretinal dan kadang-kadang dengan
neovaskularisasi choroidal sekunder pada maculopathy.
Kami melaporkan kasus akut chorioretinitis bilateral berat yang berhubungan dengan
penyebaran H. capsulatum pada remaja imunokompeten di daerah endemik. Chorioretinitis
tersebut tidak merespone pada pemberian terapi antijamur sistemik, namun kedua penyakit
sistemik dan lesi mata terobati dengan penambahan steroid sistemik.
Pengenalan
Histoplasmosis adalah endemic, mikosis sistemik yang disebabkan oleh jamur dimorfik
Histoplasma Capsulatum. Bentuk miselium dari mikroorganisme umumnya ditemukan dalam
debu dan tanah di daerah lembah Sungai Mississippi dan lembah Sungai Ohio. Sekitar 70%
penduduk yang hidup di daerah endemik yang terkena jamur dan bereaksi positif terhadap test
kulit histoplasmin antigen. Infeksi primer ini biasa di sebabkan karena inhalasi spora. Perjalanan
penyakit sangat tergantung pada jumlah microconidiae yang terhirup dan status kekebalan dari
host. Pada host yang imunokompeten, infeksi primer cenderung tidak menunjukkan gejala atau
ringan dan biasanya remits spontan.
Beberapa pasien terjangkit Presumed Ocular Histoplasmosis Syndrome (POHS), yang
berhubungan dengan temuan trias klasik berikut: Bukti perkembangan, sebelum korioretinitis
dari perifer chorioretinal bekas luka dan atrofi peripapillary, dan pada sebagian kecil pasien,
neovaskularisasi choroidal sekunder pada jaringan parut chorioretinal. Sebaliknya, bentuk
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
2/17
penyebaran progresif penyakit ini biasanya terlihat pada pasien dengan inhalasi spora besar
atau immunodeficiency. Kasus fulminan dapat terjadi dengan gangguan pernapasan, syok,
koagulasi intravaskular diseminata, dan kegagalan multi organ.
Tes diagnostik yang berguna mencakup tes serologis untuk antibodi anti-histoplasma dan
antigen polisakarida Histoplasma (HPA), noda perak pada bagian jaringan atau cairan tubuh,
dan kultur darah, sumsum tulang, cairan bronchoalveolar lavage, dan jaringan atau cairan
tubuh lainnya diduga terinfeksi berdasarkan temuan klinis. Amfoterisin B dan itrakonazol yang
paling sering digunakan untuk mengobati infeksi secara klinis signifikan.
Kami melaporkan kasus yang tidak biasa dari acute ocular histoplasmosis dan penyebaran
infeksi pada remaja imunocompetent dengan keterlibatan beberapa organ, termasuk
korioretinitis bilateral untuk terapi antijamur sistemik. Manifestasi klinis akut dari penyakit
teratasi dengan penambahan terapi steroid sistemik.
Laporan Kasus
Seorang bocah 16 tahun Afrika Amerika berobat kepada dokter anak dengan riwayat dua
minggu malaise umum, lesi kulit berjerawat, dan floaters bilateral, buruk di mata kiri. Dia
diobati dengan klindamisin untuk infeksi bakteri yang diduga menimbulka demam tinggi
spiking-(Tmax 105 F), dispnea, dan keadaan memburuk sehingga rawat inap. Pasien tidak
sedang dalam penggunaan obat lainnya saat datang berobat ke Rumah Sakit Anak LeBonheur di
Memphis, Tennessee. Catatan medis penyakit lalunya dan catatan medis pada mata biasa saja.
Pada awal pemeriksaan ophthalmologis, ketajaman visual tidak dikoreksi adalah 20/20 pada
mata kanan dan 20/20-3 di mata kiri. Pergerakan extraokular dan tekanan intraokular adalah
normal, kedua reflek pupil baik. Pada pemeriksaan slit lamp, ditemukan dua keratic presipitat
berukuran kecil pada kornea kiri. Pada pemeriksaan fundus, mata kanan pasien menunjukkan
saraf optik , kutub posterior, dan pembuluh darah yang normal. Ada dua daerah kecil
chorioretinitis, ukuran diameter disk sekitar 1 / 4, di pinggiran inferotemporal tanpa atasnya
vitritis. Mata kiri menunjukkan penyebaran, chorioretinitis multifokal melibatkan retina dan
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
3/17
koroid di kutub posterior dan pinggiran, dengan kumpulan putih seperti salju di pinggiran
hidung. Intravena angiografi fluorescein itu sangat jinak, menunjukkan tidak adanya kebocoran
dalam tahap awal dan hanya vaskulitis ringan dibuktikan dengan pewarnaan selubung
perivaskular dan fokus di tahap selanjutnya, dengan temuan hanya peradangan retina yang
minimal di samping dari fokus Choroidal terbesar (Gambar 1 ).
Pasien awalnya dirawat selama tiga hari dengan vankomisin dan klindamisin untuk infeksi
bakteri yang diduga sebelumnya. Kultur darah negatif, dan antibiotik dihentikan. Sejak
pemeriksaan ophthalmologis yang mengarah jamur sebagai penyebabnya, diberikan
amfoterisin B intravena liposomal 375 mg sekali / hari dimulai bersama-sama dengan asiklovir
intravena 750 mg dua kali / hari, sambil menunggu hasil serologi. Titer serologi Histoplasma
oleh fiksasi komplemen yang ditunjukkan untuk menjadi nyata meningkat (1:512, positif> 1:8).
Selanjutnya, H. capsulatum M-band pengujian kembali positif, menunjukkan infeksi aktif atau
baru terinfeksi. Asiklovir dihentikan setelah 3 hari, dan amfoterisin B dengan vorikonazol mulai
diberikan. Selama pengobatan dengan antimikroba, kondisi pasien terus memburuk, dengan
demam tinggi dan gangguan pernapasan meningkat.
Terjadi efusi pleura bilateral, sehingga membutuhkan drainase cairan. Tes diagnostik cairan
pleura mengungkapkan transudate, negatif untuk bakteri atau jamur, termasuk H. capsulatum.
Pemeriksaan lebih lanjut rematologi ekstensif negatif. Pemeriksaan imunologi berupa IgA, IgG,
IgM, dan IgE serta jumlah darah putih normal dan diferensial memberikan hasil normal.
Pemeriksaan lebih lanjut mengungkapkan penyakit menular HIV yang negatif serologi dengan
ELISA. Pengujian lebih lanjut adalah negatif untuk toksoplasmosis, tuberkulosis, sarkoidosis, dan
sifilis. Biopsi dari lesi kulit menunjukkan folikulitis pustular, negatif untuk bakteri atau jamur,
termasuk H. capsulatum. Meskipun satu minggu terapi antimikroba termasuk terapi antijamur
sistemik, kondisi pasien terus memburuk dan steroid intravena dimulai. Pasien menanggapi
dengan cepat terhadap pengobatan steroid, dengan resolusi demam dan perbaikan dalam
gejala pernapasan nya dalam waktu dua belas jam. Pasien diizinkan pulang beberapa hari
kemudian dengan pemberian obat itrakonazol dan obat prednison selama enam minggu dosis
tapering off.
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
4/17
Pasien terlihat di Eye Institute Hamilton satu bulan setelah presentasi awal dan tercatat hanya
memiliki satu focal spot sisa dari chorioretinitis yg aktif dalam retina perifer mata kiri. Tiga
bulan kemudian pasien asimtomatik, ada resolusi lengkap dari semua lesi aktif dengan hanya
retinal pigmen epitel (RPE) perubahan ini (Gambar 2). Atrofi epitel pigmen retina yang
dihasilkan jauh lebih kecil dari yangdiharapkan untuk tingkat chorioretinitis dilihat pada presentasi
awal, dan tidak "menekan keluar" bekas luka chorioretinal.
Gambar 1
A. Kutup posterior dari mata kiri pada saat presentasi menunjukkan fokus inflamasi tersebar
dan kabut vitreous ringan.
B. Resolusi peradangan setelah perawatan.
C. Mata kiri pada presentasi menunjukkan banyak diskrit dan lesi chorioretinitis multifokal di
pinggiran hidung pertengahan (panah kuning).
D. Fluorescein angiogram dari bidang yang sama menunjukkan hanya kebocoran pewarna jejak
di lokasi lesi padat (panah kuning).
http://www.djo.harvard.edu/files/9278_1567.jpg -
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
5/17
Gambar 2
A. Pertengahan pinggiran-inferior dari mata kiri pada saat presentasi menunjukkan penyebaran
lesi diskrit dan lesi multifocal chorioretinitis.
B. Resolusi peradangan di bidang yang sama setelah pengobatan. Sebuah bekas luka RPE yang
sudah ada sebelumnya ditampilkan di lapangan (lingkaran kuning). Hanya jejak perubahan RPE
(putih persegi) dan selubung pembuluh darah (kuning panah) terlihat di lokasi lesi padat setelah
resolusi, sebagian besar lesi diselesaikan tanpa bukti perubahan pigmen atau bekas luka.
C. Superior pertengahan pinggiran mata kiri pada saat presentasi.
D. Mata kiri setelah resolusi lesi chorioretinal menunjukkan tidak ada perubahan jaringan parutdi akhir (panah putih menandai titik cabang pembuluh darah).
Diskusi
Manifestasi okular dari histoplasmosis diduga menghasilkan hasil jaringan parut fokal
chorioretinal setelah infeksi sistemik dan respon inflamasi mereda. Temuan umum termasuk
http://www.djo.harvard.edu/files/9279_1567.jpg -
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
6/17
menekan keluar lesi chorioretinal atropi, atrofi peripapillary, dan tidak adanya peradangan
vitreous. Neovaskularisasi Choroidal adalah penyebab paling umum kehilangan penglihatan dan
diperkirakan mempengaruhi dari 5% dari mata yang terkena. Multifocal korioretinitis
diperkirakan terjadi pada pasien dengan kekebalan yang cukup untuk melokalisasi dan
merespon terhadap infeksi H. capsulatum.
Lesi chorioretinal umumnya kecil (
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
7/17
pasien ini memiliki HLA-B7 atau HLA-DRw2 histokompatibilitas kompleks antigen (1,3) H.
capsulatum. Telah diamati tidak memiliki kultur dari mata enucleated pasien yang terkena.
Pada pasien imunokompeten seperti ini, mungkin korioretinitis merupakan proses kekebalan
yang dimediasi. Telah diusulkan bahwa mekanisme ini dimediasi kekebalan korioretinitis adalah
deposisi antigen di koroid dari fokus paru atau lainnya. Untuk sebagian besar kasus, yang
menyelesaikan korioretinitis spontan dan antijamur dan atau sistemik steroid pengobatan
mungkin tidak diperlukan. Pasien kami adalah imunokompeten tetapi gagal untuk merespon
terhadap terapi antijamur sistemik, namun, ia menanggapi secara dramatis untuk terapi
steroid, menunjukkan proses penyakit terutama kekebalan dimediasi.
Dalam presentasi kasus yang tidak biasa seperti ini, hasil pemeriksaan sistemik menyeluruh
harus dilakukan untuk menyingkirkan penyebab lain dari uveitis granulomatosa multifokal
posterior, termasuk uveitis simpatik, TB, toksoplasmosis, sarkoidosis, dan proses infeksi dan
inflamasi lainnya. Status imunologi pasien merupakan pertimbangan penting dalam
menentukan diagnosis diferensial, pemeriksaan berikutnya, dan manajemen.
Presentasi penyakit pada pasien ini sangat asimetris, hanya dengan fokus perifer beberapa di
mata kanan, tetapi parah, disebarluaskan, dan penyakit multifokal di mata kiri. Perbedaanteropong tersebut dapat menjelaskan asimetri bekas luka POHS sering terlihat pada pasien
yang tinggal di daerah endemik. Meskipun adanya lesi multifokal chorioretinal di mata kiri,
pasien tidak mengembangkan luka klasik chorioretinal atrofik biasanya terkait dengan POHS.
Kami tidak, bagaimanapun, mengidentifikasi area yang jarang dari perubahan pigmen pada
tingkat RPE di lokasi fokus chorioretinal paling parah (Gambar 2B, D).
Acute systemic histoplasmosis associated with chorioretinitis in an immunocompetent adolescent
Digital Journal of Ophthalmology 2011
Volume 17, Number 3
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
8/17
August 16, 2011
Brian T. Fowler, MD* | Department of Ophthalmology, Hamilton Eye Institute, Memphis,
Tennessee
Christopher Shen, MD* | Department of Ophthalmology, Hamilton Eye Institute, Memphis,
Tennessee
Joseph Mastellone | Department of Ophthalmology, Hamilton Eye Institute, Memphis, Tennessee
Edward Chaum, MD | Departments of Ophthalmology and Pediatrics, Hamilton Eye Institute and
University of Tennessee Health Science Center, Memphis, Tennessee
Abstract
Histoplasmosis is an endemic, systemic mycosis caused by the dimorphic fungus Histoplasma
capsulatum. A minority of patients develop asymptomatic chorioretinitis known as presumed
ocular histoplasmosis syndrome (POHS), which is typically associated with chorioretinal scarring
and peripapillary atrophy and occasionally with choroidal neovascularization secondary to
maculopathy. We report a case of acute severe bilateral chorioretinitis associated with
disseminated H. capsulatumin an immunocompetent adolescent boy living in an endemic area.
The chorioretinitis did not respond to systemic antifungal therapy, but both his systemic illness
and ocular lesions resolved with the addition of systemic steroids.
Introduction
Histoplasmosis is an endemic, systemic mycosis caused by the dimorphic fungus Histoplasma
capsulatum. The mycelial form of the microorganism is commonly found in the dust and soil of
the Mississippi River valley and Ohio River valley regions.(1) Approximately 70% of the
population living in endemic areas are exposed to the fungus and react positively to a
histoplasmin skin antigen challenge.(2) Primary infection is usually due to spore inhalation. The
course of the disease largely depends on the number of inhaled microconidiae and the immune
status of the host. In immunocompetent hosts, primary infection tends to be asymptomatic or
mild and usually remits spontaneously.(1) Some patients develop presumed ocular
mailto:[email protected]:[email protected] -
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
9/17
histoplasmosis syndrome (POHS), which is associated with the following classic triad of findings:
evidence of a prior chorioretinitis, development of peripheral chorioretinal scars, and
peripapillary atrophy, and, in a small proportion of patients, choroidal neovascularization
secondary to chorioretinal scarring.(3) In contrast, the disseminated progressive form of the
disease is typically seen in patients with massive spore inhalation or immunodeficiency.
Fulminant cases can present with respiratory distress, shock, disseminated intravascular
coagulation, and multiple organ failure.(1) Useful diagnostic tests include serologic tests for
anti-Histoplasma antibodies and Histoplasma polysaccharide antigen (HPA), silver stains of
tissue sections or body fluids, and cultures from blood, bone marrow, bronchoalveolar lavage
fluid, and other tissues or bodily fluids suspected to be infected based on clinical findings.(3,4)
Amphotericin B and itraconazole are most frequently used to treat clinically significant
infections.
We report an unusual case of acute ocular histoplasmosis and disseminated infection in an
immunocompetent adolescent presenting with multiple organ involvement, including bilateral
chorioretinitis refractory to systemic antifungal therapy. The acute clinical manifestations of the
disease resolved with the addition of systemic steroid therapy.
Case report
A 16-year-old African American boy presented to his pediatrician with a two-week history of
general malaise, pustular skin lesions, and bilateral floaters, worse in the left eye. He was
treated with clindamycin for presumed bacterial infection until the onset of high-spiking fevers
(Tmax105F), dyspnea, and worsening malaise prompted hospitalization. The patient was on no
other medications at the time of admission to LeBonheur Childrens Hospital in Memphis,
Tennessee. His past medical and past ocular history were unremarkable.
On initial ophthalmological examination, uncorrected visual acuity was 20/20 in the right eye
and 20/20-3 in the left eye. Extraocular motility and intraocular pressure were normal, and the
pupils were equally reactive. The anterior segment slit-lamp examination was unremarkable
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
10/17
with the exception of two small fine keratic precipitates on the left cornea. On dilated fundus
examination, the patients right eye showed a normal-appearing optic nerve, posterior pole,
and vasculature. There were two small areas of chorioretinitis, approximately 1/4 disc diameter
in size, in the inferotemporal periphery without overlying vitritis. The left eye showed a
disseminated, multifocal chorioretinitis involving the retina and choroid in the posterior pole
and periphery, with snow-banking in the nasal periphery. Intravenous fluorescein angiography
was remarkably benign, demonstrating an absence of leakage in the early phase and only a mild
vasculitis evidenced by perivascular sheathing and focal staining in later phases, with findings of
only minimal retinal inflammation at the site of the largest choroidal foci (Figure 1).
The patient was initially treated for three days with vancomycin and clindamycin for presumed
bacterial infection. Blood cultures were negative, and antibiotics were discontinued. Since the
ophthalmological examination was suggestive of fungal etiology, intravenous liposomal
amphotericin B 375 mg once/day was started together with intravenous acyclovir 750 mg
twice/day, pending serology results. Histoplasma serology titers by complement fixation were
demonstrated to be markedly elevated (1:512, positive >1:8). Further, H. capsulatumM-band
testing returned positive, indicating active or recent infection. Acyclovir was discontinued after
3 days, and amphotericin B with voriconazole was initiated. During treatment withantimicrobials, the patients condition continued to worsen, with high fevers and increasing
respiratory distress. The etiology was large bilateral pleural effusions, requiring drainage of
fluid. Diagnostic testing of the pleural fluid revealed a transudate, negative for bacteria or fungi,
including H. capsulatum. Further extensive rheumatologic workup was negative. Immunologic
workup revealed normal IgA, IgG, IgM, and IgE as well as a normal white blood count and
differential. Infectious disease workup further revealed negative HIV serology by ELISA. Further
testing was negative for toxoplasmosis, tuberculosis, sarcoidosis, and syphilis. Biopsy of the skinlesions showed pustular folliculitis, negative for bacteria or fungus, including H. capsulatum.
Despite one week of antimicrobial therapy including systemic antifungal therapy, the patients
condition continued to worsen and intravenous steroids were started. The patient responded
rapidly to steroid treatment, with resolution of fever and improvement in his respiratory
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
11/17
symptoms beginning within twelve hours. The patient was discharged several days later on
itraconazole and a six-week prednisone taper.
The patient was seen at the Hamilton Eye Institute one month following his initial presentation
and was noted to have only one focal spot of residual active chorioretinitis in the peripheral
retina of the left eye. Three months later the patient was asymptomatic; there was complete
resolution of all active lesions, with only subtle retinal pigment epithelial (RPE) changes present
(Figure 2). The resultant retinal pigment epithelium atrophy was far less than would be
expected for the degree of chorioretinitis seen at initial presentation, and no punched out
chorioretinal scars developed.
Figure 1
A, Posterior pole of the left eye at the time of
presentation showing scattered inflammatory
foci and mild vitreous haze. B, Resolution of
the inflammation after treatment. C, Left eye
at presentation showing many discrete and
multifocal chorioretinal lesions in the nasal
mid-periphery (yellow arrows). D,
Fluorescein angiogram of the same field
showing only trace dye leakage at the sites of
denser lesions (yellow arrows).
http://www.djo.harvard.edu/files/9278_1567.jpg -
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
12/17
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
13/17
immunocompetent siblings.(8) Our patient presented with symptomatic active chorioretinitis
prior to the development of severe systemic pulmonary and dermatologic disease. The lesions
seen on the initial fundus examination were consistent with chorioretinal lesions seen in
previous case reports; however, the chorioretinitis described in our patient was unusual in that
it was more severe, diffuse, and also associated with significant systemic disease
manifestations. Interestingly, the multifocal choroidal lesions did not scar and form the classic
punched out choroidal lesions typically described in POHS. This mirrors the relatively benign
findings seen on the initial fluorescein angiography.
POHS is considered "presumed" ocular histoplasmosis because the causal relationship between
the fungus and the eye disease has not been definitively proven. In immunocompromised
patients, disseminated chorioretinitis due to H. capsulatumduring the active phase of infection
has previously been described in the literature, with ocular histopathological examination
confirming the presence of budding yeast characteristic of H. capsulatumin the choroid, retina,
and central retinal vein.(3) A reproducible model of histoplasma choroiditis may be induced in
primates by the injection of live H. capsulatumorganisms via the internal carotid artery. In this
model, variation in the severity of disease correlates with the size of innoculum and site of
injection.(9) In a review of the clinical spectrum and treatment of classic histoplasmosis, theincidence of chorioretinitis is estimated to be between 1 to 10% in endemic areas,
predominantly affecting patients between 30 and 40 years of age. Most of these patients
possess the HLA-B7 or HLA-DRw2 histocompatibility complex antigen.(1,3) H. capsulatumhas
neither been observed nor cultured from the enucleated eyes of affected patients. In
immunocompetent patients such as these, chorioretinitis may be an immune-mediated
process. It has been proposed that the mechanism of this immune-mediated chorioretinitis is
secondary to deposition of antigens in the choroid from pulmonary or other foci.(1,3) For themajority of cases, the chorioretinitis resolves spontaneously and antifungal and/or systemic
steroid treatment might not be required. Our patient was immunocompetent but failed to
respond to systemic antifungal therapy; however, he responded dramatically to steroid
therapy, suggesting a primarily immune-mediated disease process.
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
14/17
In unusual case presentations such as this, a thorough systemic workup should be undertaken
to exclude other causes of multifocal granulomatous posterior uveitis, including sympathetic
uveitis, tuberculosis, toxoplasmosis, sarcoidosis, and other infectious and inflammatory
processes. The patients immunologic statusis an important consideration in determining the
differential diagnosis, subsequent workup, and management.
The disease presentation in this patient was remarkably asymmetric, with just a few peripheral
foci in the right eye, but severe, disseminated, and multifocal disease in the left eye. Such
binocular disparity may account for the asymmetry of POHS scars commonly seen in patients
living in endemic areas. Despite the presence of multifocal chorioretinal lesions in the left eye,
the patient did not develop the classical atrophic chorioretinal scars typically associated with
POHS. We did, however, identify rare areas of pigmentary changes at the level of the RPE at the
site of the most severe chorioretinal foci (Figure 2B, D).
Literature Search
PubMed (1980 to present) and Google Scholar were searched using the following keywords:
histoplasmosis, chorioretinitis, and retina.
*These authors contributed equally to this work.
Acknowledgments
Supported in part by an unrestricted UTHSC departmental grant from Research to Prevent
Blindness, New York, NY, the Plough Foundation, Memphis, TN, and the UTHSC Hamilton Eye
Institute NEI Core Grant for Vision Research (P30 EY013080). Dr. Chaum is an RPB Senior
Scientist.
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
15/17
LAMPIRAN
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
16/17
-
8/14/2019 Acute systemic histoplasmosis associated with chorioretinitis in an.docx
17/17