Xavier University – Ateneo de Cagayan

Dr. Jose P Rizal School of Medicine

Maria Reyna- Xavier University Hospital
Department of Internal Medicine

“Don’t Take My Breath Away”

A Case Presentation on Pneumocystis Pneumonia
General objectives:
1) To present a case of a 25 year old male who came in due to shortness of breath.

Specific objectives:
1) To present an approach to patient who came in due to shortness of breath.
2) To present the epidemiology, pathophysiology and pathogenesis of Human Immunodeficiency
Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS).
3) To present the pathogenesis, clinical manifestations, diagnosis and management of Pneumocystis
Pneumonia as a complication of HIV/AIDS.

GENERAL DATA
A case of JD, 25 year old male, Filipino, Roman Catholic, single, currently unemployed, from Purok
1, Kalubihon, Dalifuga, Iligan City. This is his first hospital admission in this institution. The source of
information was the patient himself with 95% reliability.

CHIEF COMPLAINT: Shortness of breath

HISTORY OF PRESENT ILLNESS

1 month prior to admission (PTA), patient had sudden onset of on and off cough, productive of
yellowish sputum, non-blood streaked, approximately ¼ cup per day. No associated fever, dyspnea, weight
loss, or vomiting. Self-medicated with Dextromethorphan HBr + Phenylephrine HCl + Paracetamol (Tuseran)
325mg 1 tab BID with partial relief, only when cough was intolerable, about 3 to 4 days a week. Patient
tolerated his condition. No consult was done.
In the interim, there was persistence of on and off cough. Patient continued self-medicating with
Tuseran 1 tab BID. Still, no consult was done.
14 days PTA, there was onset of fever, documented at 38.4oC, usually occurring around 4:00 to
5:00 in the afternoon, associated with shortness of breath on more than ordinary activities and still with
intermittent cough, productive of yellowish sputum. No vomiting, headache, abdominal pain or chest pain.
Self-medicated with Phenylephrine HCl + Chlorphenamine Maleate + Paracetamol (Bioflu) 10/2/500mg
tablet, 1 tab daily taken in the afternoon with temporary relief. No consult was done.
13 days PTA, patient was already afebrile but there was persistence of cough and shortness of
breath. Still, no consult was done.
12 days PTA, there was noted recurrence of fever, undocumented and worsening of shortness of
breath upon climbing 5 steps of stairs. No associated headache, dizziness or vomiting. Self-medicated with
Phenylephrine HCl + Chlorphenamine Maleate + Paracetamol (Bioflu) 10/2/500mg tablet, 1 tab daily taken
in the afternoon with temporary relief. No consult was done.
9 days PTA, persistence of condition prompted consult with an Internist at Adventist Medical
Center, where CBC was done which showed normal WBC of 8.49 with neurtophilic predominance of 85%.
Chest X-ray was also done which revealed Pneumonia, as claimed by the patient. Patient was prescribed
with Cefixime (Tergicef) 400mg 1 tab OD for 7 days, Levofloxacin (Levocin) 500 mg 1 tab OD after lunch for
7 days, Montelukast + Levocetirizine (Co-altria) 10/5mg 1 tab OD for 7 days, Multivitamins (Neurogen-E)
tablet 1 tab OD for 15 days and was sent home. The following morning, there was increasing severity of
shortness of breath upon exertion and still with intermittent fever hence admission at Adventist Medical
Center, where he was managed for Pneumonia, to consider Pulmonary Tuberculosis. Patient claimed his
condition did not improve in said hospital and went home against medical advice after 4 hospital days with

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take-home medications of Cefixime 400 mg tablet 1 tab BID for 10 days, Fluconazole 50mg capsule 1 cap
OD for 7 days, Azithromycin (Natrapharm) 500 mg tablet 1 tab OD for 10 days, Cotrimoxazole 800mg tablet
1 tab BID for 10 days and Prednisone 20 mg tablet 1 tab BID after meals for 10 days with good compliance.
Patient was advised to undergo HIV counselling.
4 days PTA, patient was afebrile but still with occasional productive cough, yellowish sputum and
shortness of breath on exertion upon climbing 5 steps of stairs. Patient continued taking take-home
medications. No consult was done.
2 days PTA, patient sough consult at City Hospital TB DOTS, sputum AFB was done with pending
results. There was noted recurrence of fever in the afternoon that day. Patient self-medicated with
Paracetamol 500 mg 1 tab every 4 hours taken for fever along with the prescribed home medications.
1 day PTA, patient went for HIV counselling and testing at City Health. Patient lost consciousness
upon learning he was reactive to initial HIV screening, but regained consciousness after 1 minute. He noted
shortness of breath even during changing clothes, with undocumented fever and occasional productive
cough. Persistence and worsening of condition prompted consult and subsequent admission.

PAST MEDICAL HISTORY

The patient has no history of Hypertension, Diabetes mellitus, Bronchial asthma, Pulmonary
Tuberculosis or Malignancies. He has no past hospitalizations or surgeries.

FAMILY HISTORY
The patient has a familial history of hypertension from his paternal side, and a history of thyroid
and heart disease from his maternal side.

PERSONAL AND SOCIAL HISTORY

The patient is a non-smoker, an alcoholic beverage drinker, drinking approximately 6 liters 2-3
times a week. He has no history of illicit drug use. He claims to be bisexual in orientation, with 5 male and
1 female partner. His coitarche was at 20 years old. Patient claims he practices anal and oral sex without
protection. He has had a regular sexual partner for the past 2 years, with their last sexual encounter on
March 2018.

REVIEW OF SYSTEMS
General: No unintentional weight loss, no loss of appetite, weakness, or fatigue
Skin: No rashes, itching, changes in hair and nails.
Head: No headache or dizziness
Eyes: No blurring of vision
Ears: No difficulty hearing, tinnitus, vertigo, or otalgia
Nose and sinuses: No nasal stuffiness, discharge or itching, or epistaxis
Throat: No dysphagia or odynophagia
Neck: No stiffness
Respiratory: No colds, no hemoptysis
Cardiovascular: No orthopnea, no palpitations, no chest pain or discomfort
Gastrointestinal: No abdominal pain or changes from normal bowel movement, no melena or
hematochezia
Genitourinary: No dysuria, hematuria, or penile discharges
Endocrine: No heat or cold intolerance, no tremors, no palpitations
Hematologic: No easy bruisability or active bleeding
Neurology: No seizures, loss of consciousness or changes in behaviour

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PHYSICAL EXAMINATION

General survey
Patient is examined on the first hospital day.

Patient is awake, conscious, well-dressed, sthenic built with supplemental oxygen at 4LPM via nasal
cannula. He is oriented, cooperative, lying supine and in respiratory distress, able to speak in phrases.

Vital signs
Blood pressure: 90/60 mmHg
Pulse rate: 110 bpm
Respiratory rate: 26 cpm
Temperature: 38.2oC, Left axilla
O2 sat: 90% at O2 inhalation 4LPM
Anthropometrics
Height: 165 cm
Weight: 81 kg
BMI: 29.75 kg/m2 (Asia-Pacific Classification: Obese class 1)

Skin
Inspection:
Patient has brown skin. There are no rashes, bruises, ulcerations, cyanosis or jaundice noted. No
palmar erythema, spider angiomata noted.

Palpation:
Skin is warm to touch with smooth texture. There is good skin turgor and no tenderness noted.

Nails
Inspection:
He has pink nail beds on both upper and lower extremities. No nail clubbing and indentions.
Palpation:
Capillary refill time <2 seconds on all extremities.
HEENT
Inspection:
Normocephalic, no facial asymmetry.
Hair is short, fine, black and evenly distributed. There are no lesions seen on the scalp.
He has anicteric sclera and pink palpebral conjunctivae.
No nasal discharge.
Dry lips and moist oral mucosa. No oral lesions.
No tonsillopharyngeal enlargement.
Non-distended neck veins noted. No visible mass and pulsations.
Palpation:
There are no masses, no tenderness or lymphadenopathy noted.

Chest and Lungs

Inspection:

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 Thorax is symmetrical. There is equal chest expansion with no chest lag and intercostal/ subcostal
retractions. No lesions, lumps and masses noted.
Palpation:
Normal tactile and vocal fremeti in both lung fields.
Percussion:
Resonant lung fields.
Auscultation:
There were fine rales, bibasal, more on the right. Bronchophony, egophony, whispered
pectoriloquy are all absent.

Cardiovascular System
Inspection:
He has adynamic precordium. Point of maximal impulse is noted at the 5th intercostal space,
midclavicular line, left.
Palpation:
There are no thrills and heaves noted. Apex beat felt at the 5th intercostal space, midclavicular line,
left.
Auscultation:
He has distinct s1 and s2, tachycardic with regular rhythm. No murmurs noted.

Abdomen
Inspection:
Abdomen is flabby with no visible veins, pulsations, or lesions.
Auscultation:
Normoactive bowel sounds at 12/clicks per minute.
Percussion:
Tympanitic except over the area of the liver. Liver span is 8cm, midclavicular line.
Palpation:
No tenderness on both light and deep palpation. There is no hepatomegaly and spleen is not
palpable. No masses noted.

Genitourinary system
Inspection:
Grossly male. Multiple papulonodular lesion of varying sizes, pinkish to brown in color, located on
the dorsal and lateral shaft and base of the penis. No ulcers or scars noted on the glans, shaft and base of
the penis as well as on scrotal surface. No penile discharges noted.

Palpation:
No tenderness, induration noted on the penile area. No tenderness or swellings on the scrotum.
No inguinal lymphadenopathy.

Extremities
Inspection:
No lesions and no edema. No deformities.

Peripheral vascular system

Palpation:

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 There are full pulses on all extremities.

Brachial Radial Popliteal Dorsalis Pedis Posterior Tibial

Right 2+ 2+ 2+ 2+ 2+
Left 2+ 2+ 2+ 2+ 2+

Musculoskeletal System
Inspection:
He has good symmetric muscle bulk and tone. No deformities, atrophies, spasticity and joint
swelling noted.

Nervous System
Mental State: Oriented to time, place, and persons and responds appropriately.

Cranial Nerves:
CN I: Not assessed
CN II: Visual acuity and Visual fields intact.
CN III, IV, VI: No ptosis. Extraocular movements were intact.
CN V: Able to open and close mouth. Can identify light touch on both cheeks, forehead and
mandibular area. Positive Corneal reflex.
CN VII: Able to raise eyebrows; no facial asymmetry noted.
CN VIII: Able to hear whispers and spoken words on both ears.
CN IX, X: Able to swallow, no deviation in uvula, intact gag reflex.
CN XI: Able to shrug both shoulders against resistance, able to turn head left and right.
CN XII: Tongue protrudes at midline.
Motor:
Right Left

Upper Extremity 5/5 5/5

Lower Extremity 5/5 5/5

Cerebellar: Able to do rapid alternating movements; able to do finger to nose; normal gait
Sensory: Intact sensation on light touch, pain, temperature and pin prick.
Reflexes:

Meningeal signs: (-) Brudzinski’s sign

(-) Kernig’s sign
(-) Babinski’s sign

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SALIENT FEATURES

HISTORY PHYSICAL EXAMINATION

 25-year old, Male, Single  BP: 90/60 mmHg, HR: 110 bpm,
 Alcoholic beverage drinker RR:26cpm, Temp: 38.2oC
 Bisexual in orientation  Equal chest expansion
 5 male sexual partners  Normal tactile and vocal fremiti, right
 Unprotected anal and oral sexual basal lung field
practices  (+) Fine rales, bibasal, more on the right
 Productive cough for 1 month, yellowish  Brochophony, egophony, whispered
sputum pectoriloquy are not present
 Intermittent fever with highest recorded
temperature of 38.4oC
 Shortness of breath upon climbing 5 steps
of stairs
 Chest x-ray: Pneumonia
 Reactive on initial HIV screening

APPROACH TO DSYPNEA
Dyspnea is a subjective experience of breathing discomfort that consist of qualitatively distinct
sensations that vary in intensity. Evaluation of patients with dyspnea includes history which should be
described in the patient’s own words, physical examination to further investigate, and laboratory
procedures to confirm the findings.
An algorithm for the evaluation of patient presenting with dyspnea starts with history taking,
considering the quality of sensation, timing, positional disposition and whether dyspnea is intermittent or
persistent1. In relation to this case, it is important to note that the patient is already experiencing
intermittent productive cough of 1 month duration associated with progressive dyspnea and fever which
usually occurred in the afternoon. Patient noticed his dyspnea was persistently progressive, aggravated
upon febrile episodes and upon exertion of 5 stair steps. Patient was recently admitted, managed as a case
of CAP-MR, however went home against medical advice due to unimproved condition. Patient was Reactive
upon initial HIV testing.
After taking the history, it is important to perform a thorough physical examination. Evidence of
increased work of breathing like supraclavicular retractions; use of accessory muscles of ventilation; and
the tripod position indicate stiffness of the lungs or the chest wall1. The patient was examined in distress,
able to speak in phrases. No retractions, use of accessory muscles or tripod position. During the general
examination, signs of anemia, cyanosis, and cirrhosis should be sought. This patient has pink palpebral
conjuctivae, no pallor, palmar erythema, nor spider angiomata noted.
Examination of the chest should focus on symmetry of movement; palpation of both tactile and vocal
fremitus, percussion and auscultation1. In this case, the patient has symmetrical chest, equal chest
expansion, normal tactile and vocal fremiti and bibasal rales, more on the right which makes it likely that
there is a pulmonary etiology of dyspnea.
The cardiac examination should focus on signs of elevated right heart pressures, left ventricular
dysfunction and valvular disease1. The patient doesn’t have jugular venous distention, JVP is 7cmH2O, no
s3 or s4 gallops and no murmurs heard. This may indicate that a cardiac cause of dyspnea is less likely.
When examining the abdomen, paradoxical movement of the abdomen should be noted which is a
sign of diaphragmatic weakness and rounding of the abdomen that suggest pulmonary edema 1 which are
both absent in the patient, making pulmonary edema less likely.

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 Examination of the extremities should take note of edema, cyanosis, any deformities, as well as
clubbing of digits, which is an indication of interstitial pulmonary fibrosis1. For this patient, examination of
the extremities were unremarkable.
After a thorough history taking and physical examination, possible diagnosis may be evident. For this
case we are highly considering a pulmonary cause of the dyspnea given the pertinent physical findings of
chest and lungs. However, further evaluation can be done through chest radiograph where cardiac size,
any evidence of CHF, hyperinflation, possible pneumonia, interstitial lung disease and pleural effusion can
be assessed to aid in narrowing the differentials diagnosis and most importantly to arrive at the correct
diagnosis. ECG and echocardiography, pulmonary function testing, and haematocrit and thyroid function
tests may be utilized to further narrow down or confirm the diagnosis. If still uncertain, cardiopulmonary
exercise test may be used1.

FORMULATION
Presented with a case of 25-year old male, who came in due to shortness of breath, with history of
5 male sexual partners with unprotected anal and oral sexual practices, productive cough for 1 month with

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yellowish sputum, intermittent fever associated with reactive result in initial HIV screening and upon
physical examination, the patient was tachycardic at 110bpm, tachypneic at 26cpm, febrile at 38.2 C, with
equal chest expansion, normal tactile and vocal fremiti, bibasal fine rales, more on the right and absence
of bronchophony, egophony and whispered pectoriloquy.

DIFFERENTIAL DIAGNOSIS

Diagnosis Rule In Points Against

(+) Shortness of breath (-) Night sweats
(+) Productive cough for 1 (-) Hemoptysis
month (-) Weight loss
(+) Intermittent fever
(+) Tachypnea Cannot totally rule out
1) Pulmonary Tuberculosis
(+) Bibasal Rales

(+) Shortness of breath (+) Intermittent fever

2) Interstitial lung disease
(+) Tachypnea (-) Non-productive cough
(+) Bibasal Rales

(+) Shortness of breath on (-) Bipedal edema

exertion (-) Orthopnea
3) Acute Heart Failure
(+) Tachypnea (-) Paroxysmal nocturnal
(+) Bibasal Rales dyspnea
(-) Chest pain

PRIMARY WORKING IMPRESSIONS

1) Pneumocystis Pneumonia
2) HIV Clinical Stage III
3) Genital Warts

TIMELINE – COURSE IN THE WARDS

AT THE ER Patient was examined awake, conscious, and in respiratory distress. Vital signs
were taken which revealed a BP of 110/70 mmHg, HR of 132bpm, RR of 30cpm,
Temperature of 37.6C and O2sat of 70% @ room air.

The patient was started with a venoclysis of PNSS 1L at 30 gtts/min. Diagnostics

were ordered as follows: CBC with Platelet count which revealed leucocytosis of
18.41x109/uL with neutrophilic predominance of 89.80% and other differential
count are as follows: low lymphocyte count (7.30) and platelet count of 483,000/uL.
He was started on Piperacillin-Tazobactam 4.5 g IV every 6 hours, Levofloxacin 750
mg IV every 24 hours, Cotrimoxazole 400/80 mg tab, 2 tablets TID, and Prednisone

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 40 mg tab 1 tab BID. O2 support was ordered via nasal cannula at 2-4 LPM. The
patient was ordered with a diet as tolerated at 1500 kCal/day in 3 divided meals
and 2 snacks with strict aspiration precaution, with a distribution of 60%
carbohydrates, 20% protein and 20% fats.
Problem #1: Pneumocystis Pneumonia (PCP), Human Immunodeficiency Virus (HIV)

Hospital Day 1 Patient was seen awake, coherent, in respiratory distress. Patient had productive
cough with yellowish phlegm and complained of shortness of breath. He was noted
to be tachycardic at 100 bpm, tachypneic at 26 cpm, febrile at 38.2 C, with an O2sat
of 85% under O2 support via nasal cannula. Patient was on PNSS 2L at 20 gtts/min,
with an input of 2900 ml and an output of 2640 ml. Physical examination showed
anicteric sclerae, pink palpebral conjuctivae, and pupils equally round and reactive
to light and accommodation; equal chest expansion, bibasal rales (more on the
right); adynamic precordium, regular rhythm, with no murmurs; flabby abdomen,
normoactive bowel sounds, soft, non-tender; full peripheral pulses with no edema;
muscle strength of 5/5 in all extremities. Laboratory findings revealing leukocytosis
of 18.41 x103/ul with predominant neutrophils of 89.80%, low hematocrit count of
36.70%, and a high platelet count of 483 x103/ul; an elevated BUN of 35.43, and
creatinine of 0.72; Chest X-ray AP view revealed fine reticular and alveolar densities
seen within both lungs suggesting bilateral Pneumonia.

The assessment was Pneumocystis Pneumonia and Community Acquired

Pneumonia-high risk with hypoxemia. Patient was advised to have arterial blood gas
tests, HIV screening, Sputum GeneXpert test, CD4 count (or T-cell test), SGOT and
SGPT, repeat CBC with platelet count, and blood and sputum GS/CS. Medications
ordered from the ER were continued. Paracetamol 300 mg IV every 4 hours as
needed for fever was administered. Patient was noted to have episodes of
desaturation and was nebulized with Salbutamol + Ipatropium bromide, and was
advised to change nasal cannula to face mask 02 support at 8L per minute.
Nebulization was advised every 6 hours. Vital signs monitoring was ordered every
30 minutes to monitor episodes of desaturation.

Hospital Day 2 Patient had shortness of breath and occasional cough productive yellowish phlegm,
no febrile episodes. Medications ordered were continued. On the 3rd hospital day,
patient shortness of breath improved but still with occasional cough. No febrile
episodes noted. Equal chest expansion was noted but with findings of rales on both
lung fields, more on the right. Blood chemistry was requested revealing
unremarkable FBS, cholesterol, and triglycerides. Complete blood count revealed
leukocytosis of 14.12 x103/ul with predominant neutrophil of 94.30% and elevated
platelet count of 553 x103/ul. Patient was advised to have Chest Xray-PAL and
Ultrasound of the whole abdomen. Medications were continued.
Hospital Day 4 Shortness of breath improved but still with coughing episodes. Upon physical
examination, patient’ rales on both lung fields decreased but noted decreased
breath sounds on bibasal lung fields. X-ray of the chest taken in PAL view revealed
minimal progression of previously noted air space opacities in both lungs suggesting

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 worsening bilateral Pneumonia. Microbiology examination of blood after 3 days
incubation revealed no growth. Medications were continued.
Hospital Day 5 to 8 Patient’s shortness of breath and cough improved. Upon physical examination,
patient rales decreased but decreased breath sounds were still noted on bibasal
lung fields. On the 8th hospital day, Salbutamol + Ipatropium bromide nebulization
every 15 minutes for 3 doses was ordered, then every 8 hours. Other medications
were continued.
Problem #2: Genital Warts

Hospital Day 1 During physical examination, the patient was noted to have multiple papulonodular
lesions of varying sizes, rounded in shape on the dorsal aspect of the penis. No
associated tenderness on the affected area, no ulcers, scars, nodules, or signs of
inflammation noted on the skin, foreskin, glans and base of the penis as well as on
scrotal surface. No discharges noted. The lesions were identified as genital warts.
No medications were ordered for this.

Hospital Day 2 to 9 Genital lesions were still noted without any change in number, distribution, location
and characteristics of the lesions and without any associated symptom. Still, no
medication was ordered for the lesion.

Problem #3: Oral Thrush

Hospital Day 4 Patient noticed to have onset of oral lesion located in the soft palate. There was no
associated pain at the site of the lesions, itchiness, difficulty swallowing or any bad
taste sensation. The lesions were characterized as thick small annular plaques, few
in number having asymmetric distribution localized in the soft palate, with well-
defined borders, creamy white in color, non-erythematous, about 3 mm in greatest
dimension without bleeding or exudates. The lesions were then identified as oral
thrush. Fluconazole 200 mg 1 tab once a day was then started. Other medications
were continued.

Hospital Day 5 On the 5th hospital day, still with no pain, itchiness, difficulty swallowing or any
change in taste sensation was noted. The lesions had increased in number now
affecting the buccal and inner lip mucosa as well having a 6 mm greatest dimension,
without bleeding or exudates. Fluconazole was continued.

Hospital Day 7 On the 7th hospital day, oral thrush was still present with no associated pain,
itchiness, difficulty swallowing or any change in taste sensation. The lesions were
noted to have decreased in number, now only affecting the soft palate and buccal
mucosal area without extension to the pharyngeal area. Ongoing medications were
continued. No new medication was added.

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 Hospital Day 8 On the 8th hospital day, oral thrush was still noted without any associated
symptoms. The lesions became localized in the soft palate, few in number without
redness, bleeding or exudates. Fluconazole was still continued.

Hospital Day 9 On the 9th hospital day, complete resolution of the lesion was noted. No
pain, itchiness, or redness was noted. Fluconazole was still continued.

On the 8th hospital day, oral thrush was still noted without any associated symptoms. The lesions
became localized in the soft palate, few in number without redness, bleeding or exudates. Fluconazole
was still continued.

On the 9th hospital day, complete resolution of the lesion was noted. No pain, itchiness, or redness
was noted. Fluconazole was still continued.

CASE DISCUSSION

I. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS)

Epidemiology
HIV infection is a global pandemic, with cases reported from virtually every country. At the end
of 2013, an estimated 35.0 million individuals were living with HIV infection1 . An estimated 95% of
people living with HIV/AIDS reside in low and middle-income countries; ~50% are female, and 3.2 million
are children <15 years. In 2013, an estimated 2.1 million new cases of HIV infection occurred worldwide,
including 240,000 among children <15 years; about 40% of new infections were among persons under
age 25.
The HIV epidemic has occurred in “waves” in different regions of the world, each wave having
somewhat different characteristics depending on the demographics of the country and region in
question and the timing of the introduction of HIV into the population.
In Asia and the Pacific, an estimated 4.8 million people were living with HIV at the end of 2013. In
this region of the world, HIV prevalence is highest in Southeast Asian countries, with wide variation in
trends between different countries.

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 In the Philippines2, there were 924 new HIV antibody seropositive individuals reported to the
HIV/AIDS & ART Registry of the Philippines (HARP). Nineteen percent (179) had clinical manifestations
of advanced HIV infection (WHO clinical stage 3 or 4) at the time of diagnosis. Ninety-six percent (885)
of the newly diagnosed were male. The median age was 28 years old and half (50%) were 25-34 years
old at the time of testing. About one third (30%) were from National Capital Region and less than 1%
were from ARMM. Sexual contact remains the predominant mode of transmission. Among this, eight-
six percent were males who have sex with males (MSM). Other mode of transmission was needle sharing
among injected drug users (1%).

According to Health and Care Today Clinic of

NMMC3, as of June 2018, a total of 751 patients
registered to their hub and 566 patients are actively registered. Out of the 646 registered HIV patients
in HACT NMMC, only 553 are active on ART, the remaining were are active on ART under other HACT
hubs and the rest were lost to follow-up.

Pathophysiology and Pathogenesis

HIV infection is a profound immunodeficiency resulting primarily from a progressive quantitative

and qualitative deficiency of the subset of T lymphocytes referred to as helper T cells occurring in a
setting of polyclonal immune activation. The CD4 molecule present on these cells along with co-
receptors, CCR5 and CXCR4 are required for fusion and entry, and subsequent replication of the virus.
A number of mechanisms responsible for cellular depletion and/or immune dysfunction of CD4+
T cells have been demonstrated in vitro; these include direct infection and destruction of these cells by
HIV, as well as indirect effects such as immune clearance of infected cells, cell death associated with
aberrant immune activation, and immune exhaustion due to aberrant cellular activation with resulting
cellular dysfunction. HIV is transmitted primarily by sexual contact (both heterosexual and male to
male); by blood and blood products; and by infected mothers to infants intrapartum, perinatally, or via
breast milk. It has been demonstrated that sexual transmission of HIV is the result of a single infectious
event. In the early events of HIV infection, access of HIV with mucosal transmission facilitate viral entry
and increase the efficiency of infection. Both partially” resting CD4+ T cells and activated CD4+ T cells
serve as early amplifiers of infection. Resting CD4+ T cells are more abundant; however, activated CD4+
T cells produce larger amounts of virus.

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 Once infection is established, the virus replicates in lymphoid cells in the mucosa, the submucosa,
and to some extent the lymphoreticular tissues that drain the gut tissues. In acute HIV syndrome, which
occurs in ~50% of individuals, acute mononucleosis-like symptoms are well correlated with the presence
of Viremia. Once infection has been established the virus succeeds in escaping complete immune-
mediated clearance, paradoxically seems to thrive on immune activation, and is never eliminated
completely from the body. Most patients are relatively asymptomatic while this progressive decline of
CD4 T cells is taking place and are often described as being in a state of clinical latency. A chronic
infection develops and persists with varying degrees of continual virus replication in the untreated
patient for a median of ~10 years before the patient becomes clinically ill. It is this establishment of a
chronic, persistent infection that is the hallmark of HIV disease. Once patients reach CD4+ T cell levels
below a critical level of (<200/μL), they are at high risk of developing a variety of opportunistic diseases,
For this reason, the CDC case definition of AIDS includes all HIV-infected individuals over 5 years of age
with CD4+ T cell counts below this level. The depletion of CD4+ T cells continues to be progressive and
unrelenting in this phase.

II. Pneumocystis pneumonia (PCP)

Epidemiology
Pneumocystis pneumonia (PCP) remains the most prevalent opportunistic infection in patients
infected with the human immunodeficiency virus (HIV). 4 PCP is caused by Pneumocystis jirovecii, an
organism classified as a fungus but also shares biologic characteristics with protozoa. Pneumocystis
spreads by the airborne route, occurring by new acquisition or reactivation of infection. 5
The incidence of PCP has declined substantially with widespread use of PCP prophylaxis and
antiretroviral therapy (ART), compared before when PCP occurred in 70% to 80% of patients with AIDS,
and these patients were associated with a 20% to 40% mortality rate in individuals with profound
immunosuppression. 6
Approximately 90% of PCP cases occurred in patients with CD4 T-lymphocyte (CD4 cell) counts
<200 cells/mm3. Higher risk of PCP includes CD4 cell percentage <14%, previous episodes of PCP, oral
thrush, recurrent bacterial pneumonia, unintentional weight loss, and higher plasma HIV RNA levels.

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Most cases occur in patients who are unaware of their HIV infection or are not receiving ongoing care
for HIV, and in those with advanced immunosuppression (CD4 counts <100 cells/mm3). 7

Clinical Manifestations
Pneumocystis pneumonia is often the AIDS-defining illness in patients infected with HIV,
occurring most frequently when the T-helper cell count (CD4+) is less than 200 cells per cubic
millimeter. 4 In HIV-infected patients, the most common manifestations of PCP are sub-acute onset of
progressive 4dyspnea, fever, non-productive cough, and chest discomfort that worsens within days to
weeks. The fulminant pneumonia observed in patients who are not infected with HIV is less common.
In mild cases, pulmonary examination usually is normal at rest. With exertion, tachypnea, tachycardia,
and diffuse dry rales may be observed. 8
Oral thrush is a common co-infection. Fever is apparent in most cases and may be the
predominant symptom in some patients.9 Hypoxemia, the most characteristic laboratory abnormality,
can range from mild (room air arterial oxygen [pO2] ≥60 mm Hg) to moderate (40-59 mm Hg) to severe
(<40 mm Hg). Elevation of lactate dehydrogenase levels to >500 mg/dL is common but non-specific. 7
Chest radiograph typically demonstrates bilateral perihilar interstitial infiltrates that become
increasingly homogeneous and diffuse as the disease progresses. Less common findings include solitary
or multiple nodules, upper-lobe infiltrates in patients receiving aerosolized pentamidine,
pneumatoceles, and pneumothorax. Pleural effusions and thoracic lymphadenopathy are rare. 8
Spontaneous pneumothorax in a patient with HIV infection should raise the suspicion of approximately
13% to 18% of patients with documented PCP have another concurrent cause of pulmonary
dysfunction, such as tuberculosis (TB), Kaposi sarcoma (KS), or bacterial pneumonia. 7

Diagnosis
The principal definitive diagnosis for Pneumocystis infection remains direct visualization of the
pathogen by various staining techniques such as the Grocott-Gomori methenamine silver (GMS),
Wright-Giemsa, calcofluor white, and the Papanicolaou stains.10 Spontaneously expectorated sputum
has low sensitivity and should not be submitted to the laboratory to diagnose PCP.
Direct and indirect immunofluorescent stains that utilize antibodies directed against the
organism are also commonly used.12 GMS selectively stains the wall of Pneumocystis cysts and can be
used on smears or tissue (Fig. 1). Wright-Giemsa stains all stages of the parasite and works best with
cytologic smears. Calcofluor white is a chemifluorescent agent that nonspecifically binds to the b-linked
polymers of the cell wall and can be used with tissue or smears. The Papanicolaou stain highlights the
eosinophilic material surrounding the organism known as a ‘‘foamy body’’ but does not stain individual
organisms clearly.10
Previous studies of stained respiratory tract samples obtained by various methods indicate the
following relative diagnostic sensitivities: induced sputum <50% to >90% (the sensitivity depends on
the pathogen load and specimen quality, while the specificity depends on the experience of the
microbiologist or pathologist), bronchoscopy with BAL 90% to 99%, transbronchial biopsy 95% to 100%,
and open lung biopsy 95% to 100%.7
Patients with AIDS and pneumocystis pneumonia have a significantly increased number of
pneumocystis organisms in their lungs, with fewer neutrophils, than do patients with pneumocystis
pneumonia in the absence of AIDS. This greater organism burden results in a higher diagnostic yield of
induced sputum and bronchoalveolar lavage fluid to confirm pneumocystis pneumonia in patients with
AIDS as compared with other conditions associated with immunosuppression.8
Polymerase chain reaction (PCR) is an emerging method for diagnosing PCP. The sensitivity of
PCR for bronchoalveolar lavage appears to be high; the ability of PCR to distinguish colonization from

15
 disease is less clear. 1,3s-D-glucan (a component of fungal cell walls) may be elevated in patients with
PCP, but the assay’s sensitivity and specificity for establishing a PCP diagnosis are problematic, and
other fungal diseases can produce elevation.7
Because certain processes produce similar clinical manifestations, a specific diagnosis of PCP
should be sought rather than relying on a presumptive diagnosis, especially in patients with moderate-
to-severe disease.7
Treatment can be initiated before making a definitive diagnosis because organisms persist in
clinical specimens for days or weeks after effective therapy is initiated.11

Management

Trimethoprim- Sulfamethoxazole (TMP-SMX) is the treatment of choice for PCP.10 The dose
must be adjusted for abnormal renal function. 13 Adding leucovorin to prevent myelosuppression during
acute treatment is not recommended because efficacy is questionable and some evidence exists for a
higher failure rate. Oral outpatient therapy with TMP-SMX is highly effective in patients with mild to
moderate disease.14 Alternative therapeutic regimens for mild-to-moderate disease include: dapsone
and TMP which may have efficacy similar to TMP-SMX and fewer side effects, but is less convenient
because of the number of pills; primaquine plus clindamycin; and atovaquone suspension, which is less
effective than TMP-SMX for mild-to-moderate disease but has fewer side effects. Whenever possible,
patients should be tested for glucose-6-phosphate dehydrogenase deficiency before primaquine or
dapsone is administered. 7
Alternative therapeutic regimens for patients with moderate-to-severe disease include
clindamycinprimaquine or IV pentamidine. Some clinicians prefer clindamycin-primaquine because of
its higher degree of efficacy and lesser toxicity compared with pentamidine. Aerosolized pentamidine
should not be used to treat PCP because its efficacy is limited and it is associated with more frequent
relapse.
Mutations associated with resistance to sulfa drugs have been documented, but their effect on
clinical outcome is uncertain. Patients who have PCP despite TMP-SMX prophylaxis usually can be
treated effectively with standard doses of TMP-SMX. Patients with documented or suspected PCP and
moderate to severe disease, defined by room air pO2 <70 mm Hg or Alveolar-arterial O2 gradient ≥35
mm Hg, should receive adjunctive corticosteroids as early as possible and certainly within 72 hours
after starting specific PCP therapy. Methylprednisolone at 75% of the respective prednisone dose can
be used if parenteral administration is necessary. 7

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 The recommended duration of therapy for PCP is 21 days.15 The probability and rate of
response to therapy depend on the agent used, number of previous PCP episodes, severity of
pulmonary illness, degree of immunodeficiency, timing of initiation of therapy and comorbidities. 7
The overall prognosis remains poor for patients who have such severe hypoxemia that
admission to an intensive care unit (ICU) is necessary. However, in recent years, such patients have
had much better survival than in the past, perhaps because of better management of comorbidities
and better supportive care. Because long-term survival is possible for patients in whom ART is
effective, individuals with AIDS and severe PCP should be offered ICU admission or mechanical
ventilation if their functional status is such that it would be appropriate, just as with HIV-uninfected
patients. In patients not on ART, ART should be initiated, when possible, within 2 weeks of diagnosis
of PCP. 7

Monitoring of Response to Therapy and Adverse Events

In patients with AIDS, rates of adverse reaction

to TMP-SMX are high (20%–85%). Common adverse
effects are rash (30%–55%) (including Stevens-
Johnson syndrome), fever (30%–40%), leukopenia
(30%–40%), thrombocytopenia (15%), azotemia (1%–
5%), hepatitis (20%), and hyperkalemia. Supportive
care for common adverse effects should be
attempted before TMP-SMX is discontinued. Rashes
often can be “treated through” with antihistamines,
nausea can be controlled with antiemetics, and fever
can be managed with antipyretics. 7
The most common adverse effects of
alternative therapies include methemoglobinemia
and hemolysis with dapsone or primaquine (especially
in those with G6PD deficiency); rash and fever with dapsone; azotemia, pancreatitis, hypo- or
hyperglycemia, leukopenia, electrolyte abnormalities, and cardiac dysrhythmia with pentamidine;
anemia, rash, fever, and diarrhea with primaquine and clindamycin; and headache, nausea, diarrhea,
rash, and transaminase elevations with atovaquone. 7

Managing Treatment Failure

Intravenous pentamidine is generally considered a second-line agent for severe disease or for
patients who fail primary therapy with TMP-SMX10, clinical failure defined as lack of improvement or
worsening of respiratory function documented by arterial blood gases (ABGs) after at least 4 to 8 days
of anti-PCP treatment. Failure attributed to lack of drug efficacy occurs in approximately 10% of those
with mild-to-moderate disease. No convincing clinical trials exist on which to base recommendations
for the management of treatment failure attributed to lack of drug efficacy. Clinicians should wait at
least 4 to 8 days before switching therapy for lack of clinical improvement. 7
In the absence of corticosteroid therapy, early and reversible deterioration within the first 3 to
5 days of therapy is typical, probably because of the inflammatory response caused by antibiotic-
induced lysis of organisms in the lung. Other concomitant infections must be excluded as a cause of
clinical failure; bronchoscopy with BAL should be strongly considered to evaluate for this possibility,
even if the procedure was conducted before initiating therapy. 7
Switching to another regimen is the appropriate management for treatment-related toxicity.
When TMP-SMX is not effective or cannot be used for moderate-to-severe disease because of toxicity,

17
the common practice is to use parenteral pentamidine or oral primaquine combined with intravenous
clindamycin. Cohort studies concluded that the combination of clindamycin and primaquine might be
the most effective regimen for salvage therapy, although no prospective clinical trials have evaluated
the optimal approach to patients who experience a therapy failure with TMP-SMX. 7

REFERENCES:

1. Kasper, D. and Harrison, T. (2015). Harrison's principles of Internal Medicine. New York: McGraw-
Hill, Medical Pub. Division.
2. Department of Health – Epidemiology Bureau. HIV/ AIDS & ART Registry of the Philippines. April
2018.
3. Census of Health and Care Today Clinic, NMMC Treatment Hub. July 2018.
4. 10. Thomas CF, Limper AH. Medical Progress: Pneumocystis pneumonia. Thoracic Diseases
Research Unit, Division of Pulmonary and Critical Care Medicine, Department of Internal
Medicine(C.F.T., A.H.L.), and the Department of Biochemistry and Molecular Biology (A.H.L.),
Mayo Clinic College of Medicine, Rochester, Minn. The New England Journal of Medicine.
Copyright © 2004 Massachusetts Medical Society. Downloaded from nejm.org on July 22, 2018.
5. Pifer LL, Hughes WT, Stagno S, Woods D. Pneumocystis carinii infection: evidence for high
prevalence in normal and immunosuppressed children. Pediatrics. Jan 1978;61(1):35-41.
Available at http://www.ncbi.nlm.nih.gov/pubmed/400818.
6. Buchacz K, Baker RK, Palella FJ, Jr., et al. AIDS-defining opportunistic illnesses in US patients, 1994-
2007: a cohort study. AIDS. Jun 19 2010;24(10):1549-1559. Available at
http://www.ncbi.nlm.nih.gov/pubmed/20502317.
7. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the
prevention and treatment of opportunistic infections in HIV-infected adults and adolescents:
recommendations from the Centers for Disease Control and Prevention, the National Institutes
of Health, and the HIV Medical Association of the Infectious Diseases Society of America.
Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed July 18,
2018.
8. Selwyn PA, Pumerantz AS, Durante A, et al. Clinical predictors of Pneumocystis carinii pneumonia,
bacterial pneumonia and tuberculosis in HIV-infected patients. AIDS. May 28 1998;12(8):885-893.
Available at http://www.ncbi.nlm.nih.gov/pubmed/9631142.
9. Ng VL, Yajko DM, Hadley WK. Extrapulmonary pneumocystosis. Clin Microbiol Rev. Jul
1997;10(3):401-418. Available at http://www.ncbi.nlm.nih.gov/pubmed/9227859.
10. D’Avignon LC, et al. Pneumocystis pneumonia. Infectious Disease Service, San Antonio Military
Medical Center, Fort Sam Houston, Texas. Published by Thieme Medical Publishers, Inc., 333
Seventh Avenue, New York, NY 10001, USA.Downloaded July 20, 2018.
11. Roger PM, Vandenbos F, Pugliese P, et al. Persistence of Pneumocystis carinii after effective
treatment of P. carinii pneumonia is not related to relapse or survival among patients infected
with human immunodeficiency virus. Clin Infect Dis. Feb 1998;26(2):509-510. Available at
http://www.ncbi.nlm.nih.gov/pubmed/9502487.
12. Procop GW, Hadda S, Quinn J, et al. Detection of Pneumocystis jiroveci in respiratory specimens
by four staining methods. J Clin Microbiol 2004;42:3333–3335
13. Hughes W, Leoung G, Kramer F, et al. Comparison of atovaquone (566C80) with trimethoprim-
sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med.
May 27 1993;328(21):1521-1527. Available at http://www.ncbi.nlm.nih.gov/pubmed/8479489.

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14. Safrin S, Finkelstein DM, Feinberg J, et al. Comparison of three regimens for treatment of mild to
moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized,
trial of oral trimethoprimsulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine.
ACTG 108 Study Group. Ann Intern Med. May 1 1996;124(9):792-802. Available at
http://www.ncbi.nlm.nih.gov/pubmed/8610948.
15. Kovacs JA, Hiemenz JW, Macher AM, et al. Pneumocystis carinii pneumonia: a comparison
between patients with the acquired immunodeficiency syndrome and patients with other
immunodeficiencies. Ann Intern Med. May 1984;100(5):663-671. Available at
http://www.ncbi.nlm.nih.gov/pubmed/6231873.

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