Stephanie Strollo

Swine influenza (H1N1): Diagnostic dilemmas early in the pandemic

Recognizing and diagnosing cases of influenza A in adults during the influenza season is relatively straightforward. This year, the swine influenza H1N1 pandemic began at the end of the usual influenza season (December 2008 March 2009). Swine influenza H1N1 appears to have started in Veracruz, Mexico, quickly spreading to other parts of Mexico, then to the USA, Europe and other parts of the world. In New York, the first recognized cases were at a school in New York City. The pandemic quickly spread to surrounding areas during April May 2009 [1]. A pandemic alert was declared by the Centers for Disease Control and Prevention (CDC) and hospitals in affected areas activated pandemic influenza plans, as we did at our hospital. Our institution mobilized its resources in accordance with the Health Department and CDC interim recommendations for emergency department (ED) triage for influenza A (QuickVue) screening. Specimens of respiratory secretions of patients that tested positive for influenza A were sent to the Health Department/CDC for reverse transcriptase polymerase chain reaction (RT-PCR) swine influenza H1N1 testing [2,3]. We implemented a prioritized response plan for the allocation of negative pressure and ventilator rooms, and devised plans for furloughing of employees who were sick or in contact with probable cases of swine influenza H1N1. Criteria were developed for oseltamivir (Tamiflu) prophylaxis/therapy [4,5]. A special multidisciplinary emergency task force was activated to handle the pandemic potential. In spite of these preparations, during the initial weeks of the swine influenza H1N1 pandemic, we found ourselves inundated with patients with influenza-like illnesses (ILIs) presenting to the ED for rapid influenza A testing. We experienced diagnostic difficulties related to rapid influenza A false negative screening tests. The other rapid influenza diagnostic tests (RIDTs), i.e., respiratory fluorescent antibody (FA) viral tests, did not agree with results of rapid influenza A testing. Without definitive RT-PCR results, difficulties with clinical diagnosis, i.e., overdiagnosing and misdiagnosing, quickly became apparent. Definitive testing for swine influenza H1N1 by RT-PCR was restricted resulting in a lack of definite diagnoses in most patients. Our initial experience with swine influenza H1N1 may be viewed as an learning experience and cautionary tale for a potential future wave (fall 2009 and/ or winter/spring 2010) of more virulence/severity, as occurred in the 1918 1919 influenza pandemic [6,7]. Our recent early experience demonstrated major problem areas with the laboratory and clinical diagnoses of swine influenza H1N1.

Severe swine influenza A (H1N1) versus severe human seasonal influenza A (H3N2): Clinical comparisons

At the beginning of the swine influenza (H1N1) pandemic in the spring of 2009, there were still stories of human seasonal influenza A circulating in the New York area. Adult patients admitted with influenza-like illnesses (ILIs) (fever > 102°F, dry cough, and myalgias) presented diagnostic problems. First, clinicians had to differentiate ILIs from influenza, and then differentiate human seasonal influenza A from H1N1 in hospitalized adults with ILIs and negative chest films (no focal segmental/lobar infiltrates). Human seasonal influenza A was diagnosed by rapid influenza diagnostic tests (RIDTs), but H1N1 was often RIDT negative. Reverse transcriptase-polymerase chain reaction for H1N1 was restricted or not available. The Winthrop-University Hospital Infectious Disease Division developed clinical diagnostic criteria (a diagnostic weighted point score system) to rapidly and clinically diagnose H1N1 in patients with negative RIDTs. The point score system was modified and shortened for ease of use, that is, the diagnostic H1N1 triad (any 3 of 4) (ILI, see above) plus thrombocytopenia, relative lymphopenia, elevated serum transaminases, or an elevated creatine phosphokinase. Our clinical experience during the pandemic allowed us to develop the swine diagnostic H1N1 triad. In the process, similarities and differences between human seasonal influenza A and H1N1 were noted. We present 2 illustrative cases of severe influenza, one due to human seasonal influenza A and one due to H1N1, for clinical consideration reflective of our experiences early in the H1N1 pandemic in 2009.

Fever of unknown origin (FUO): de Quervain's subacute thyroiditis with highly elevated ferritin levels mimicking temporal arteritis (TA)

Fever of unknown origin (FUO) refers to prolonged fevers of > or = 101 degrees F and that persists for > 3 weeks that remain undiagnosed after an intensive in-hospital/outpatient workup. The most common FUO categories of are infectious, neoplastic, rheumatic/inflammatory, and miscellaneous causes. Malignancies have supplanted infectious diseases as the most common cause of FUOs in the adult population. Rheumatic/inflammatory causes of FUO are relatively less common than previously because of the introduction over the years of sophisticated diagnostic tests for most rheumatic diseases. The rheumatic/inflammatory disorders that remain important causes of FUO today are those that cannot be readily diagnosed by readily available/noninvasive tests, for example, adult Stills disease and temporal arteritis (TA). In older patients with FUO, TA can be a difficult diagnosis when the characteristic findings (ie, scalp tenderness, jaw claudication) are not present. Patients with TA presenting as FUO often have only headaches that may be accompanied by bilateral jaw discomfort. Endocrine causes of FUOs are rare. The most common endocrine disorder rarely presenting as an FUO is de Quervains subacute thyroiditis. As in TA, subacute thyroiditis may present with headache and pain at the angle of the jaw. Both TA and subacute thyroiditis may be accompanied by fatigue, weight loss, and night sweats. We present a case of 55-year-old woman who presented with an FUO with clinical and laboratory findings suggesting TA. However, the absence of thrombocytosis and a normal alkaline phosphatase argued against the diagnosis of TA. Also against the diagnosis of TA was weight loss without loss of appetite and a slightly increased pulse. After nonspecific laboratory test results suggested that TA was not the cause of her FUO, additional tests were ordered. Thyroid function test results suggested the possibility of de Quervains subacute thyroiditis as the cause of her FUO. To the best of our knowledge, this is the first case of de Quervains subacute thyroiditis presenting as an FUO with elevated ferritin levels.

Swine influenza (H1N1) pneumonia: elevated serum procalcitonin levels not due to superimposed bacterial pneumonia

TCC 27853, which was between reference values [3]. For both eropenem and doripenem, the MIC90 (MIC for 90% of the organsms) of the collected strains was >64 mg/L. The MIC50 (MIC for 0% of the organisms) was also identical for the two antibitics tested (64 mg/L) (Table 1). None of the strains collected was ensitive according to CLSI criteria (susceptible ≤4 mg/L; resistant 8 mg/L) [3]. Only marginal differences in MICs of meropenem verus doripenem were found, with a maximal difference of only two ilutions (Table 1). In case of such high MICs, these differences were ot sufficient to consider treatment with doripenem in infections ith MDR Pseudomonas spp. We conclude that, as Fujimura et al. lso mentioned, although doripenem is one of the most potent and romising antipseudomonal drugs, in vitro results from our hospial suggest no role of doripenem in the treatment of infections with DR Pseudomonas spp.

Non-specific laboratory test indicators of severity in hospitalized adults with swine influenza (H1N1) pneumonia

New York was at the epicenter of the “herald wave” of the swine influenza (H1N1) pandemic in the spring of 2009 [1, 2]. Our hospital, Winthrop-University Hospital (WUH), like other hospitals in the area, were inundated with patients with influenza-like illnesses (ILIs) presenting themselves to our Emergency Department (ED) for testing and clinical evaluation. In the majority of patients, the swine influenza (H1N1) was a mild ILI not severe enough to warrant hospitalization. However, 25 adult patients were ill enough to be admitted with definite/probable swine influenza (H1N1) pneumonia during the “herald wave” of the pandemic.

Swine influenza (H1N1) pneumonia in hospitalized adults: chest film findings.

In patients with swine influenza (H1N1) pneumonia, the admission chest film is critical to rapidly detect simultaneous bacterial pneumonia due to Staphylococcus aureus or subsequent bacterial pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae by the presence of focal infiltrates. Our objective was to characterize the chest film findings in 25 adults hospitalized with H1N1 pneumonia during the pandemic and detect focal infiltrates indicative of bacterial coinfection, that is, bacterial pneumonia. Chest films were obtained on admission, after 48 hours, and thereafter as indicated throughout hospitalization. Chest film findings were classified as no infiltrates, clear with accentuated bibasilar lung markings, or focal segmental/lobar infiltrates. The presence or absence of pleural effusion and cavitation was also noted. Admitted adults with H1N1 pneumonia had negative chest films or accentuated basilar lung markings. After 48 hours, 13% of patients developed patchy bilateral interstitial infiltrates. No patients had or subsequently developed focal segmental/lobar infiltrates indicative of bacterial community-acquired pneumonia during hospitalization. The most common chest film finding was no infiltrates or an accentuation of bibasilar lung markings in hospitalized adults with H1N1 pneumonia. No patients had focal segmental/lobar infiltrates indicative of superimposed bacterial community-acquired pneumonia.

Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels

Kawasakis disease is a disease of unknown cause. The characteristic clinical features of Kawasakis disease are fever≥102°F for≥5 days accompanied by a bilateral bulbar conjunctivitis/conjunctival suffusion, erythematous rash, cervical adenopathy, pharyngeal erythema, and swelling of the dorsum of the hands/feet. Kawasakis disease primarily affects children and is rare in adults. In children, Kawasakis disease is more likely to be associated with aseptic meningitis, coronary artery aneurysms, and thrombocytosis. In adult Kawasakis disease, unilateral cervical adenopathy, arthritis, conjunctival suffusion/conjunctivitis, and elevated serum transaminases (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) are more likely. Kawasakis disease in adults may be mimicked by other acute infections with fever and rash, that is, group A streptococcal scarlet fever, toxic shock syndrome (TSS), and Rocky Mountain Spotted Fever (RMSF). Because there are no specific tests for Kawasakis disease, diagnosis is based on clinical criteria and the syndromic approach. In addition to rash and fever, scarlet fever is characterized by circumoral pallor, oropharyngeal edema, Pastias lines, and peripheral eosinophilia, but not conjunctival suffusion, splenomegaly, swelling of the dorsum of the hands/feet, thrombocytosis, or an elevated SGOT/SGPT. In TSS, in addition to rash and fever, there is conjunctival suffusion, oropharyngeal erythema, and edema of the dorsum of the hands/feet, an elevated SGOT/SGPT, and thrombocytopenia. Patients with TSS do not have cervical adenopathy or splenomegaly. RMSF presents with fever and a maculopapular rash that becomes petechial, first appearing on the wrists/ankles after 3 to 5 days. RMSF is accompanied by a prominent headache, periorbital edema, conjunctival suffusion, splenomegaly, thrombocytopenia, an elevated SGOT/SGPT, swelling of the dorsum of the hands/feet, but not oropharyngeal erythema. We present a case of adult Kawasakis disease with myocarditis and splenomegaly. The patients myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasakis disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL; (normal<189 ng/mL). To the best of our knowledge, this is the first report of adult Kawasakis disease with highly elevated serum ferritin levels. This is also the first report of splenomegaly in adult Kawasakis disease. We conclude that Kawasakis disease should be considered in the differential diagnosis in adult patients with rash/fever for≥5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels.

Fever of unknown origin (FUO) caused by Kikuchi's disease mimicking lymphoma

Fever of unknown origin (FUO) refers to infectious, neoplastic, or rheumatic/inflammatory disorders that present with fevers of 101 degrees F or greater for 3 weeks and that remain undiagnosed after an intensive in-hospital or outpatient workup. The noninfectious causes of FUO in adults are most often lymphomas or rheumatic/inflammatory disorders. Among the rare causes of rheumatic/inflammatory FUOs is Kikuchis disease. Kikuchis disease (Kikuchi-Fujimoto disease) is also known as histiocytic necrotizing lymphadenitis, a benign, self-limited disorder usually in middle-aged women of Asian descent. Cervical adenopathy is typical and often accompanied by leukopenia. In middle-aged adults patients presenting with an FUO, the presence of otherwise unexplained cervical adenopathy should suggest the possibility of lymphoma or, rarely, Kikuchis disease.