clinical presentation march 24, 13
TRANSCRIPT
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
CLINICAL PRESENTATION
Dr. Juan Carlos Díaz Torre
Pediatra Neonató[email protected]
( 779 ) 100 - 40 - 261
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
2
Rash, Pain, and Dyspnea Progressing to Respiratory Failure
A 68-year-old woman presents to the emergency department (ED) complaining of progressive shortness of breath, flank pain, fever, and weakness. A diffuse, pinkish rash that had started 6 hours before presentation is noted over her extremities and trunk.
She has a history of diabetes and has been taking glyburide irregularly, with poor glycemic control documented by blood glucometer record.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
3
About 10 days ago she noted a small ulcer on the dorsum of her left foot that started to grow in size, with associated low-grade fever and pain along her left leg. Her primary doctor prescribed her a course of amoxicillin, which she is currently taking.
She takes no other medications, does not smoke tobacco, and does not use illicit drugs or alcohol.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
4
She reports no headache, neck stiffness, nausea, vomiting, expectoration, chest pain, cough, sore throat, abdominal pain, changes in urine color, melena, hematemesis, or bleeding.
She has no medical allergies and has not recently traveled outside her home country of Cuba.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
5
On physical examination, the patient is a mildly obese female who appears very ill and is in acute distress. Pallor, mild cyanosis, poor capillary refill (3-4 sec), and a weak, rapid radial pulse are noted. She is conscious and is alert and oriented.
She has a patent airway and her respiratory rate is 30 breaths/min with bilateral rales and diminished air entry into both lung bases.
Normal S1 and S2 heart sounds are heard with no discernible murmur.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
6
She is tachycardic with a heart rate of 122 beats/min. The pharyngeal examination shows no erythema or exudate. The axillary temperature is 98.6°F (37°C). Her blood pressure is 85/50 mm Hg. No jugular venous distension is noted.
The abdominal examination is unremarkable; examination of the stool is negative for occult blood.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
7
Her skin appears plethoric and cool with a diffuse, nonvesicular, nonpalpable, petechial, non-blanching rash (see images).
A necrotic, crusted black eschar is observed on her left leg. The eschar is about 5 cm in diameter.
Neurologic examination is unremarkable and there are no signs of meningismus.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
8
Laboratory studies are ordered; these include a complete blood cell count with a hemoglobin of 14.4 g/dL (144 g/L); a hematocrit of 42% (0.42 L/L); white cell count of 7 x 103 /µL (7 x 109 /L) with a neutrophilic predominance of 79%; a platelet count of 250 × 103/µL (250 × 109/L); and a normal peripheral smear.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
9
Her coagulation studies at admission are all normal, but her creatinine is significantly elevated at 3.2 mg/dL (285 µmol/L).
Arterial blood gas analysis (with supplemental oxygen) reveals a pH of 7.10, PaO2 of 80 mm Hg, PaCO2 of 49 mm Hg, SaO2 of 90%, bicarbonate of 13 mmol/L, and a base deficit of -15.2 mmol/L.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
10
A lumbar puncture is performed, which shows a clear acellular cerebrospinal fluid with low glucose 34.8 mg/dL (1.9 mmol/L) and a normal protein level. The results of a urinalysis are normal. She is hypoglycemic, with finger stick glucose of 58.7 mg/dL (3.2 mmol/L).
Electrolyte analysis demonstrates mild hyperkalemia (5.7 mmol/L).
A chest radiograph shows changes consistent with early adult respiratory distress syndrome (ARDS).
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
11
The patient is treated in the ED with intravenous (IV) crystalloid, IV steroids, vasopressor support, and IV antibiotics.
Endotracheal intubation is performed due to worsening hypoxic respiratory failure, and the patient is placed on a mechanical ventilator; the patient is then transported to the intensive care unit.
Gram stain and blood culture samples of the skin lesions are obtained.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
12
A purpuric petechial rash is seen around the umbilical zone
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
13
The rash is disseminated all over the patient's skin, with a mild cyanotic tint.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
14
A closer view of the inguinal zone shows a purpuric unblistered rash.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
15
.
What is the diagnosis?
Hint: Consider the patient's history, leg ulcer, and described lesions.
- Henoch-Schönlein purpura
- Anaphylactic shock secondary to amoxicillin
- Waterhouse-Friderichsen syndrome
- Toxic epidermal necrolysis
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
16
. Correct answer:
- Henoch-Schönlein purpura
- Anaphylactic shock secondary to amoxicillin
- Waterhouse-Friderichsen syndrome ****
- Toxic epidermal necrolysis
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
17
While in the ICU, the patient's shock progressed in spite of high doses of vasopressors and stress doses of glucocorticoids maintained through her hospital course. Her blood coagulation profile was compatible with disseminated intravascular coagulation (DIC).
Serum cortisol was not measured because hydrocortisone was administered in the ED.
The Gram stain, skin lesion cultures, and cerebrospinal fluid cultures were all negative.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
18
In this case, the diagnosis of Waterhouse-Friderichsen syndrome (WFS) was made clinically on the basis of the patient's history and laboratory findings.
Although hypoglycemia, hypotension, and hyperkalemia could be associated with severe sepsis, acidosis, and acute renal failure, some clues suggested the WFS diagnosis, such as hypotension that does not respond to vasopressors (later confirmed in this case), skin rash, DIC, and the abrupt onset of shock.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
19
The presence of shock, DIC, skin lesions, and bilateral adrenal hemorrhage in the presence of sepsis are specific criteria for WFS.
Her history of poorly controlled diabetes, as well as the leg ulcer, aroused suspicion for bacterial infection through her skin ulcer.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
20
Blood cultures later revealed a widely susceptible (gentamicin, amikacin, ciprofloxacin, norfloxacin, meropenem, aztreonam, among others) Pseudomonas aeruginosa infection.
A CT scan of the abdomen was not performed because of the progressive deterioration of the patient's clinical condition.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
21
WFS was first described by the British physician Rupert A. Waterhouse in 1911 as "a case of suprarenal apoplexy" and by Carl Friderichsen, a Danish pediatrician, in 1918, although previous cases had been reported in the few years beforehand.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
22
WFS is generally associated with fulminant meningococcemia (Neisseria meningitides), although many other organisms have been associated with WFS, including viruses such as cytomegalovirus and HIV, parvovirus B19, and Epstein-Barr virus.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
23
Other organisms involved are bacteria such as Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Mycobacterium tuberculosis; and fungi such as Histoplasma capsulatum (among others).
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
24
Noninfectious etiologies include birth trauma, pregnancy, idiopathic adrenal vein thrombosis, bilateral metastatic adrenal malignancies, seizures, anticoagulant therapies, or following venography, trauma, and surgery.
Recently, antiphospholipid antibody syndrome has been associated with adrenal hemorrhage and infarction.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
25
Adrenal hemorrhage is a rare condition; only 10% of patients with adrenal hemorrhage develop glandular failure.
More than 90% of both glands must be destroyed before signs of adrenal insufficiency manifest; however, adrenal failure that does develop from adrenal hemorrhage is usually lethal.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
26
The fact that glucocorticoid replacement does not always prevent death in patients with adrenal hemorrhage or acute insufficiency suggests that WFS is a consequence rather than a cause.
Symptoms and signs may be diverse but are typically sudden and unexpected, sometimes without prior illness. Even with aggressive therapy, many patients die in less than 24-36 hours.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
27
Early in the course of disease, the patient may experience flank, epigastrium, and/or abdominal pain.
Complaints may include an acute onset of symptoms commencing with chills, malaise, severe headache, vertigo, vomiting, and prostration.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
28
Hours later, hypotension or collapse with agitation, delusions, and extensive areas of petechial-hemorrhagic rash appear in the mucosae and skin that may become confluent and form extensive purpuric areas ("flowers of death").
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
29
Extensive subcutaneous confluent hemorrhage known as "purpura fulminans" may also occur and is caused by DIC.
This rash is present in more than 75% of patients and usually begins as a pink, maculopapular eruption on the extremities; it also develops a petechial component that becomes ecchymotic and hemorrhagic.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
30
Petechiae often appear initially on the ankles, wrists, and in the axillae and may spread to any part of the body (including the conjunctiva); however, it tends to spare the palms, soles, and head.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
31
Despite these rather impressive clinical findings, the clinical diagnosis of WFS may be extremely challenging.
Patients who appear in the initial and nontoxic-appearing stage without any skin lesions may be difficult to distinguish from patients with benign viral illness.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
32
The pathophysiology of this syndrome is not well understood, but available evidence has implicated adrenocorticotropic hormone (ACTH), adrenal vein spasm and thrombosis, and the normally limited venous drainage of the adrenal gland.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
33
The adrenal gland has a rich arterial supply, in contrast to its limited venous drainage, which is critically dependent on a single vein.
Furthermore, in stressful situations, ACTH secretion increases, which stimulates adrenal arterial blood flow that may exceed the limited venous drainage capacity of the organ and lead to hemorrhage.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
34
In addition, adrenal vein spasm induced by high catecholamine levels secreted in stressful situations and by adrenal vein thrombosis induced by coagulopathies may lead to venous stasis and hemorrhage.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
35
The adrenal cortex produces both cortisol (a glucocorticoid) and aldosterone (a mineralocorticoid).
Cortisol maintains cardiac output, vascular resistance, and hepatic glucose output. Shock and death can occur without adequate glucocorticoids.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
36
Aldosterone modulates renal sodium reabsorption in exchange for potassium excretion.
Hyperkalemia is caused by aldosterone deficiency and/or acidosis due to shock and poor perfusion.
Immunodeficiency seems to be a predisposing condition to WFS resulting from infectious processes.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
37
Patients with splenectomy or asplenia, diabetes, organ transplantation, and those receiving chemotherapy or chronic steroids are at higher risk for septic shock and death after an infection.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
38
In WFS, a normal to slightly elevated leukocyte count with a left shift is often seen. The chemistry profile may demonstrate an elevated anion-gap metabolic acidosis secondary to lactic acid production.
If there is bilateral adrenal hemorrhage, hyponatremia, hyperkalemia, mild azotemia, leukocytosis with eosinophilia, and, occasionally, hypoglycemia may be found.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
39
The blood pressure may be abnormally low. Coagulation abnormalities may be present and may reflect ongoing DIC and consumptive coagulopathy.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
40
These abnormalities include elevated prothrombin time, partial thromboplastin time, fibrin degradation products, and decreased fibrinogen and platelets.
Low serum cortisol levels indicate relative adrenal insufficiency.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
41
A contrast-enhanced abdominal CT scan will typically demonstrate enlargement of the adrenal glands with bilateral hemorrhage.
Gram stain and cultures should be obtained from blood, cerebrospinal fluid, urine, and sputum. In a large percentage of patients, no organisms will be seen on Gram stain and cultures will not reveal any organism for more than 24 hours.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
42
Other microbiologic testing, such as wound cultures, should be directed by the clinical scenario.
Smears of petechial skin lesion scrapings should be performed. These efforts may demonstrate the pathogen in about 70% of cases.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
43
Due to the fulminant course of WFS, therapy should start as soon as the diagnosis is suspected. Initial antibiotic coverage should be broad, consisting of a third-generation cephalosporin (eg, cefotaxime, ceftriaxone) in adults.
In this case, a highly susceptible P aeruginosa strain was isolated.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
44
Antibiotics with reported antipseudomonal effects include penicillins (ticarcillin, piperacillin, piperacillin/tazobactam), cephalosporins (ceftazidime, cefepime), carbapenems (imipenem/cilastatin, meropenem, doripenem), monobactamics (aztreonam), aminoglycosides (tobramycin, gentamicin, amikacin, netilmicin), fluoroquinolones (ciprofloxacin, levofloxacin), and colimicin.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
45
However, decision making regarding specific antipseudomonal therapies should be guided by local resistance patterns.
Supportive therapy includes intravenous fluids, inotropic support, mechanical ventilation, and correction of coagulopathy and electrolyte abnormalities as needed.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
46
In adrenal crisis, the goal is to reverse the hypovolemia with crystalloid, which may be supplemented with 5% dextrose IV (given the hypoglycemia often seen in these patients).
Testing for cortisol should be obtained if adrenal dysfunction or hemorrhage is suspected, and glucocorticoids should be urgently administered.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
47
Stress-dose glucocorticoids, either hydrocortisone 50 mg every 6 hours or dexamethasone 4 mg every 12 hours can be administered. Dexamethasone does not interfere with the cortisol assay, and corticotrophin stimulation can be performed after the patient receives dexamethasone.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
48
Mineralocorticoid replacement with fludrocortisone may be indicated in patients with a history of bilateral, extensive adrenal hemorrhage in order to replace mineralocorticoid hormone requirements based on results of adrenal function testing or the clinical picture.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
49
Therapy is unnecessary in (acutely ill) patients receiving more than 100 mg of hydrocortisone daily, as this dose is thought to provide adequate mineralocorticoid replacement.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
50
In spite of adequate and aggressive treatment with fluids, glucocorticoids, antibiotic therapy, and ventilation, the patient in this case continued to decompensate and died 12 hours later due to multiorgan failure thought to be secondary to P aeruginosa septic shock.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
51
Although the antibiotic selection on admission was effective against P aeruginosa lately isolated, the initial selection of amoxicillin (which is not effective in the treatment of this bacteria) and the delay in recognizing the patient's severe sepsis may be responsible for the final outcome in this patient.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
52
The diagnosis of WFS was later confirmed via autopsy, wherein massive bilateral suprarenal and hemorrhagic effusion in other organs was observed. The adrenal glands and renal medulla had a macroscopically diffuse dark red color.
No histologic signs of immunodeficiency were found, but the liver and spleen were enlarged and friable.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
53
There were no signs of meningitis.
Rapidly progressive vascular collapse and acute respiratory failure caused by P aeruginosa septicemia (with lower extremity cellulitis/ulcer being the portal of entry) were considered responsible for the patient's multiple organ failure and cause of death.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
54
Review: You are examining an adult patient who you suspect may be manifesting WFS. Which of the following organisms would most likely be seen in this patient?
- H influenza
- M tuberculosis
- N meningitidis - Cytomegalovirus
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
55
Correct answer:
- H influenza
- M tuberculosis
- N meningitidis ****
- Cytomegalovirus
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
56
N meningitidis is the most frequent organism reported as a cause of WFS, although massive vaccination has decreased the incidence.
The other organisms have also been identified in cases of WFS.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
57
If you do in fact suspect a diagnosis of WFS in a patient you are examining, which of the following courses of action would be best?:
- Antibiotics should be prescribed but only after bacterial susceptibility confirmation
- Broad-spectrum antibiotics and supportive therapy should be initiated as soon as WFS is suspected
- Treatment should focus on normalizing the cortisol and aldosterone levels only
- The patient should be referred to radiography for chest imaging
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
58
Correct answer:
- Antibiotics should be prescribed but only after bacterial susceptibility confirmation
- Broad-spectrum antibiotics and supportive therapy should be initiated as soon as WFS is suspected ****
- Treatment should focus on normalizing the cortisol and aldosterone levels only
- The patient should be referred to radiography for chest imaging
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orre
59
Due to the fulminant course of this syndrome, therapy should be started as soon as the diagnosis is suspected.
Initial antibiotic coverage should be broad.
DR.
JCDT
Dr. Juan Carlo
s Díaz T
orreGracias por su atención
Dr. Juan Carlos Díaz Torre Pediatra Neonató[email protected]
(779) 100 - 40 - 2660