CASE CLINICAL APRIL 2011 TABASAN ELCIDA CRYPTOCOCCOISIS

aSGuest93241

Download

Post to :

URL :

Related Presentations :

Add to Flag Embed

Views: 45

Category: Science & Tech..

Presentation Description

No description available.

Comments

Presentation Transcript

DESSIMINATED CRYPTOCCOCCAL DISEASE:

DESSIMINATED CRYPTOCCOCCAL DISEASE Dimples Camporedondo MD April 29, 2011

General Data :

General Data T.E. 45 yr old Female Born Again Christian Separated , with live in partner Unemployed District 5, Purok 2 Calaanan , Canitoan Cagayan de Oro City

Chief Complaint: :

Chief Complaint: Mass at the back – surgery department a referral from Surgery department due to a Biopsy result of Cryptococcosis

History of Present Illness :

History of Present Illness A diagnosed case of Cryptococcus Meningitis last May of 2009 (NMMC)

Slide 5:

2 years prior to diagnosis episodes of on and off bouts of headache, 8/10 in severity, throbbing, generalize, associated with dizziness, body malaise, cough projectile vomiting.

Slide 6:

tolerated the condition and pain intake of pain reliever such as Mefenamic Acid 500mg with limited relief. No further consultation was done

Slide 7:

1 year prior to diagnosis repeatedly attacked with headache, which almost comes everyday and was associated with cough and low grade fever. consulted at XU-CHCC IM-OPD

Slide 8:

XUCHCC- treated as a case of Pneumonia and Sinusitis, she was prescribed with Erythromycin 500mg QID x 7 days with no relief

Slide 9:

patient’s headache worsen without other neurologic deficit, she sought consult at NMMC ER she was given Diphenhydramine 50mg IVTT, Tramadol 50mg IVTT discharged the following morning

Slide 10:

Patient condition was not alleviated Transfer at Sabal Hospital She was admitted and work up was done Lumbar pucture and CSF analysis was taken- no organisms

Slide 11:

CT-Scan – Hypodensity involving the Right basal Ganglia and Right Frontal Periventricular white matter with small round enhancing lesions (1 cm). Inflammatory pathology to r/o Multiple Sclerosis

Slide 12:

CALAS test- Cryptococcal antigen latex agglutination system revealed a positive result, which confirmed the diagnosis that the patient has Cryptococcal infection

Slide 13:

Medications were not started Financial constraints for Amphotericin B Opted medication on transfer to NMMC Fluconazole 200mg BID which was given for 2 weeks

Slide 15:

Condition improved No more headaches, dizziness, vomiting Discharged improve Advice to continue Fluconazole for 3 months but was not able to procure

Slide 16:

Patient was apparently well after anti fungal treatment Until 1 year after her admission (May 2010) noted a growing fist size soft tissue mass on her mid-back

Slide 17:

She sought consult at XUCHCC Surgery OPD (May 2010) impression was Lipoma , so an excision was scheduled Mass was excise revealing a whitish yeast appearance Cloxacillin 500mg QID x 1 week Biopsy result – pending for 2 months

Slide 18:

(Sept. 2010) noted a pain and bulging mass –on her left hip which she reconsulted with Surgery dept. X-ray of Pelvis - Spondylosis of Lumbar spine and Degenerative osteoarthropathy on both hips Biopsy Result- Chronic inflammatory reaction with abundant fungal yeast forms compatible with Cryptococcosis

Slide 19:

She was transferred to FMC service

Past Medical History :

Past Medical History Previous Hospitalization: 1982 when she was 17 years old in NMMC, due to Pneumonia No other past illnesses were noted. No operations or blood transfusion were done, and there is no history of food and drug allergy. History of exposure to pigeons

Personal and Social History :

Personal and Social History 3/7 siblings, born and raise in Cagayan de Oro City Currently unemployed, worked before as a sales agent of a lending firm separated with her husband in 1994 and they have 2 daughters, Mylene (22) and Shiela (18)

Slide 22:

live in partner since 2001, Nelson (47) a construction worker, and they have no offspring live with their 2 daughters eldest daughter is working in a department store, and her youngest daughter is a college student Her partner and some of her siblings helped her during the time of her crisis

OB-GYNE HISTORY :

OB-GYNE HISTORY menarche at eleven years old moderate flow consuming 2-3 napkins/day, with subsequent menses ate regular monthly interval not associated with dysmenorrhea . 2 sexual partners Patient is G2P2 (2002) No contraception

Family History :

Family History heridofamilial disease- HPN, DM diabetes with her mother side, who also died from the complications of DM at 74. Father is 76 and still alive, other siblings are apparently well No other history of asthma, cancer, thyroid problems and psychiatric problems

Slide 25:

GENERAL REVIEW OF SYSTEMS SKIN RESPIRATORY NECK CARDIOVASCULAR GASTROINTESTENAL GENITO URINARY PERIPHERAL/VASCULAR/MUSCULOSKELETAL NEUROLOG I C HEMATOLOGIC ENDOCRINE PSYCH I ATR I C HEENT

Slide 26:

( + ) weakness (-) fever

Slide 27:

( - ) rashes, lump, sores, itching, dryness, color change, changes in hair or nails.

Slide 28:

Head: ( + ) headache , (-) head injury, dizziness, lightheadedness Eyes: (+) blurred vision, (-) glasses or contact lenses, pain, redness, excessive tearing, double vision Ears: (-) tinnitus, vertigo, earache, infection, discharge Nose and sinuses: (-) colds, (-) nasal stuffiness, discharge or itching, nosebleeds Throat: (-) bleeding gums, sore tongue, dry mouth, sore throats, hoarseness

Slide 29:

( - ) lump, goiter, pain, stiffness

Slide 30:

( + ) cough (-) hemoptysis , dyspnea , wheezing

Slide 31:

( - ) hypertension, chest pain or discomfort, palpitations, dyspnea , orthopnea , paroxysmal nocturnal dyspnea

Slide 32:

( - ) nausea, abdominal pain (-) change in bowel movements, rectal bleeding, hemorrhoids, constipation, diarrhea, food intolerance, excessive belching, jaundice

Slide 33:

( - ) dysuria , frequency, (-) polyuria , nocturia , urgency, hematuria , incontinence, hesitancy, dribbling (-) vaginal discharge

Slide 34:

( + ) hip pain (-) leg cramps, calves pains, varicosities

Slide 35:

(-) fainting, blackouts, seizures, weakness, paralysis, numbness or loss of sensation, tingling or “pins and needles,” tremors

Slide 36:

(-) anemia, easy bruising or bleeding, transfusions

Slide 37:

( - ) heat and cold intolerance, excessive sweating, excessive thirst or hunger, polyuria

Slide 38:

( - ) depression, memory change

Slide 39:

PHYSICAL EXAMINATION

:

Conscious Coherent Ambulatory cooperative Afebrile NIRD General Survey

Slide 42:

SKIN Fair, good turgor, Nails . no clubbing, clean ridges and bands (-) jaundice, rashes Head. Atraumatic; no tenderness present; coarse black wavy evenly distributed hair. Eyes. (-) slight sunken eyeballs, Eyebrows and eyelashes evenly distributed; extraocular movements intact; conjunctivae slightly pinkish without discharge; anicteric sclerae; presence of reflex on both eyes, pupils are symmetrical, equally round, 2 mm in size constricting to 1 mm, and equally reactive to light. Ears . Acuity intact to whispered and spoken voice; no deformities, lumps or lesions; Nose and Sinuses . Nose straight without masses; nasal mucosa pink without any sign of infection; no tenderness detected over frontal and maxillary sinuses. Mouth and Throat . Lips dry and no lesions. HEENT

Slide 43:

NECK supple with full range of motion; no engorged blood vessels and scars thyroid non-tender and not enlarged no lymphadenopathy THORAX and LUNGS Inspection- No deformities, (+) lesions (open excised wound w/ draining pus on mid back) , (-) masses and chest retractions Auscultation - Vesicular breath sounds in both lung fields. No adventitious sounds

Slide 45:

CARDIOVASCULAR Adynamic precordium , distinct heart sounds normal rate regular rhythm, (-) murmurs ABDOMEN flat, soft, Normoactive bowel sounds present (-) tenderness on light and deep palpation in all quadrants (-) hepatosplenomegally

Slide 46:

GENITOURINARY (-) KPS Peripheral Vascular System and Extremities No varicosities and carotid bruit Radial, dorsalis pedis and posterior tibialis pulses present and symmetrical bilaterally

Slide 47:

MUSCULOSKELETAL Good range of motion, No joint deformities (+) Tenderness on lift hip, with 3x cm soft tissue mass

Slide 50:

Impression: Disseminated Cryptococcal Infection with Soft tissue lesions

Differential Diagnosis:

Differential Diagnosis Chief Complaint Soft tissue mass History of severe headache with no neurologic deficits Lipoma Sebaceous cyst

Work- up:

Work- up Chest X-ray – Negative Hematogram- Within normal limits Blood chemistries- Within normal limits HIV test – negative

Slide 53:

DISCUSSION

causative agent of cryptococcosis :

causative agent of cryptococcosis ubiquitous encapsulated fungus Cryptococcus neoformans . 2 pathogenic varieties are known. C. neoformans var. neoformans which, though worldwide in distribution, is found primarily in temperate areas, and C.neoformans var gattii found in the tropical and subtropical regions of Australia, Africa, America and Southeast Asia.

Slide 55:

Old, dried pigeon droppings- are the main reservoir of var. neoformans var. gattii has been isolated from Eucalyptus camaldulensis (red river gum) and more recently, from E.tereticornis (forest red gum), but has not been proven to exist in pigeon droppings

Exposure :

Exposure Ptient has potential exposure Cryptococcus. The patient had a history of having had cared for. Diamond, however asserts that no occupational predisposition exists, and the ubiquitousness of the organism, hardly makes histories of exposure to pigeons, dust or eucalyptus of much importance.

Predisposition to Cryptococcal Infection :

Predisposition to Cryptococcal Infection The fact that C. neoformans is commonly found in the environment, but rarely was known to cause human cryptococcal disease prior to the AIDS epidemic, point to a naturally high human resistance to infection and the significance of altered immune host status.

Slide 58:

HIV infection is presently the most common predisposing factor, other conditions that similarly alter host defenses , particularly cell-mediated immunity (CMI), can lead to severe cryptococcosis . conditions include collagen vascular disease (e.g. SLE), chronic corticosteroid therapy, sarcoidosis , Hodgkin's lymphoma, chronic lymphocytic leukemia , diabetes mellitus and immunosuppressive therapy aimed at T cells

Slide 59:

Cryptococcus is not known to form exotoxins and the pathology appears to be due mainly to tissue displacement by multiplying organisms. What is vital, therefore, to overcoming cryptococcal infections are intact neutrophil , macrophage and sensitized T cell function. Steroid therapy generally antedates infection.

Slide 60:

Cryptococcal infection may occur in all age groups. Considering, however, the physiologic immunocompromise that accompanies old age, this factor may have been contributory to the second patient's predisposition to severe disease.

Slide 61:

It has been reported that even apparently "normal" patients, i.e. those without identifiable immune system disorders may have subtle selective lymphocyte deficiencies

Slide 62:

Alternatively, there may be no immune derangement despite the history of exposure to pigeons; this case may actually be reflective of a var. gattii infection, which is more common in tropical regions, occurs more often in otherwise immune competent patients with cryptococcal meningitis, and has greater association with brain cryptococcomas and generally bespeaks of a better prognosis.

Pulmonary cryptococcosis :

Pulmonary cryptococcosis The respiratory tract is the most common route of entry of the organism, yet pulmonary disease does not occur in all persons found to have Cryptococcus in their airways or lungs. this may be reflective of the importance of intact immune functions in exposed individuals

Slide 64:

Pulmonary cryptococcosis may be asymptomatic. Patients with the disease may manifest with cough, chest pain, mucoid sputum, weight loss, low fever, hemoptysis , pleurisy, dyspnea , night sweats and malaise. Chest roentgenograms may not be revealing, or may show well circumscribed areas of pneumonitis

Slide 65:

Pulmonary cryptococcal disease is rarely the direct cause of mortality What is most dreaded is dissemination of the organism from a pulmonary focus to the CNS, which is quite a stealthy affair occurring even when pulmonary disease appears to be stable or resolving. In majority of reported patients, CNS involvement becomes evident when pulmonary disease had already resolved.

Meningoencephalitis :

Meningoencephalitis The most common site of dissemination in cryptococcosis is the central nervous system. Zimmermann et al. states that this predilection is because of (1) the absence in the CSF of soluble anticryptococcal factors present in serum, (2) the lack of significant activation of complement in the CSF, and (3) the abundance of excellent substrate for more virulent yeasts

Slide 67:

Dissemination to the CNS generally carries a bleak prognosis. A retrospective study done in Thailand by Schmutzhard et al proposes that cryptococcal meningoencephalitis in the Orient is different from those seen in temperate countries

Slide 68:

This is because of the different distribution of the two varieties of Cryptococcus neoformans that reported cases of cryptococcal meningoencephalitis from the tropics do not have immunocompromising conditions and usually follow a benign course

Slide 69:

Studies done on the clinical features of cryptococcal infection describe a subacute or chronic course and signs and symptoms of headache, nausea, dizziness, low fever, altered mental status, motor abnormalities, cranial nerve palsies, cerebellar signs and increase in intracranial pressure. It is best to call CNS invasion in cryptococcosis as a meningoencephalitis , as meningeal signs are hardly prominent

Slide 70:

Lumbar puncture is the most valuable diagnostic procedure in ascertaining the diagnosis of CNS cryptococcal infection. Caution, however, must be observed in the rare patient with focal neurologic deficits (as in the first patient) because these deficits may forewarn of a cryptococcoma that could risk cerebellar herniation following the lumbar tap.

Slide 71:

In these situations, a CT or MRI study of the brain may be prudent procedures to be carried out initially. In the patient’s case, a CSF analysis was normal, although there was a positive CALAS, and a significant CT scan findings

Soft Tissues :

Soft Tissues Cryptococcus in the lungs may spread hematogenously to the skin Lesions may be multiple, but usually there is only one, beginning as a painless papule, growing bigger until the center becomes shiny, flat and ulcerated with thin exudate draining.

Slide 73:

Skin lesions in cryptococcosis may be mistaken for squamous cell cancer, basal cell cancer and molluscum contagiosum ; this is especially true in HIV patients. In this patient who developed soft tissue lesions, with a biopsy findings of fungal yeast- Cryptococcus.

Cryptococcemia :

Cryptococcemia Perfect, et al's report on patients with cryptococcemia showed a one-year survival of 29%. Mortality in these patients was not always directly due to cryptococcosis , but rather secondary to underlying disease or other infections.

Slide 75:

His study, however, showed that cryptococcemia nearly always occurred in the setting of a serious underlying disease, immunosuppressive therapy and CNS involvement, and a high fungal load, hence always requiring treatment

Slide 76:

TREATMENT / GUIDELINES

Slide 77:

Factors to consider in determining the outcome of cryptococcal infection are (1) the site of infection (CNS dissemination has the gravest prognosis) (2) underlying clinical and immune disorders (3) time of initiation of therapy (4) drug efficacy

Slide 78:

Failure to treat has frequently been associated with fatal outcomes though the Campbell, et al. study accounts for 14 young and "healthy" patients with untreated cryptococcal meningitis who survived for more than two years without antifungal treatment

Amphotericin B:

Amphotericin B causes rapid sterilization of the CNS remains to be the drug of choice in treating cases of disseminated cryptococcosis Its side effect profile, however, and the need for prolonged maintenance therapy, especially among AIDS patients in whom relapses are common have prompted studies to find equally effective alternative treatment regimens

Amphotericin B:

Amphotericin B Its side effect profile, however, and the need for prolonged maintenance therapy, especially among AIDS patients in whom relapses are common have prompted studies to find equally effective alternative treatment

Flucytosine (5-FC) :

Flucytosine (5-FC) another antifungal that has activity against cryptococcosis , has been limited by development of resistance It is used in combination with amphotericin B, with which it shows synergistic effects, but with higher incidence of side effects, particularly cytopenias

Two triazole drugs, itraconazole and fluconazole:

Two triazole drugs, itraconazole and fluconazole Fluconazole available in both oral and intravenous forms have wide distribution throughout the body, attains good CSF levels and has minimal side effects

Slide 83:

Results of Larsen et al's study, however, showed that whereas patients on combination of amphotericin B, and 5-flucytosine had 100% cure rate 57% of those on fluconazole had treatment failure however, mean time to CSF sterilization was also prolonged for fluconazole (41 days), as compared to 16 days for amphotericin B an4d flucytosine.1

Itraconazole:

Itraconazole shows promise in the treatment of disseminated cryptococcosis , in particular cryptococcal meningoencephalitis Itraconazole is an oral drug with very good absorption and minimal side effects Though it does not penetrate the CSF, high plasma levels and even higher brain and meningeal levels are attained

itraconazole:

itraconazole Both in vitro and animal models have demonstrated anti- cryptococcal activity Clinical trials have also supported this affectivity.Denning , et al. reported response rates of 90% for cryptococcal meningitis, 100% for cryptococcemia (10/10), 60% for cryptococcuria (3/5), 100% for osteomyelitis (1/1), pulmonary (1/1) and soft tissue cryptococcosis (2/2). Other studies have shown patients' clinical status and drug dosage effects outcome with itraconazole therapy.

itraconazole:

itraconazole Moribund patients benefited less from itraconazole . Drug dosages of 400 mg/day have been shown to be better than a daily dose of 200 mg, and 100 mg/day is the lowest efficacious maintenance therapy. Combination regimen with 5-flucytosine, does not enhance clinical and anti- mycotic activity but merely increases the cost of treatment.

Slide 87:

Because relapses are common, it should be emphasized that repeated assessment, especially of the CSF, must be done It has been recommended that weekly lumbar taps be performed in the first six weeks of treatment.