Cases

Saddled With Siderosis

/ Cases /

A 28-year-old man comes to primary care after perusing a health website, which recommended that he get a screening evaluation for hemochromatosis. It discussed the risk associated with being of European heritage (which he is), and after reading more about it, he became anxious and wants to know if he should be checked. He does not have any of the symptoms listed on the website and does not recall family members ever discussing it. He has no significant past medical history and takes no medications.

Exam – normal

Labs – normal CBC, Chem I

Discussion

To screen or not to screen…

Primary or hereditary hemochromatosis is a disorder of iron overload resulting from genetic mutations that lead to increased iron absorption from the small intestine. Most cases (about 86%) arise from a mutation in the HFE gene (H for hereditary hemochromatosis, FE for iron) on chromosome 6. The product of this gene is a regulator of hepcidin, which in turn, regulates iron metabolism.

The most common HFE mutation is a nucleotide substitution, guanine to adenine, which causes the amino acid cysteine to be substituted by tyrosine at position 282 (C282Y). Homozygosity for the mutation is required to develop iron overload because the normal allele present in heterozygotes makes sufficient protein to overcome the deficiency from the mutant allele (autosomal recessive pattern).

A less common HFE mutation causes an amino acid change from histidine to aspartic acid at position 63 (H63D). Homozygosity is not associated with clinical disease, but compound heterozygosity (one copy each of C282Y and H63D) is associated with iron overload.

A third HFE mutation, of less clinical relevance, involves a serine-to-cysteine amino acid substitution at position 65 (S65C). Also rare are many non-HFE mutations, including hemojuvelin (HJV), hepcidin antimicrobial peptide gene (HAMP), transferrin receptor 2 (TfR2), and ferroportin (SLC40A1 – solute carrier family 40 member 1).

Approximately 10% of those with northern European ancestry are heterozygotes (carriers) for hemochromatosis, and approximately 0.4 to 0.5% are homozygotes.

The HFE mutations decrease the function of hepcidin, causing increased duodenal iron uptake, up to a few milligrams per day above normal. Although a small amount, it is enough to overwhelm normal daily iron losses of 1-1.5 milligrams. No physiologic system exists to increase iron excretion in the case of excess. The increased absorption adds between ten to forty grams of iron over the course of a few decades (normal total body iron is three to four grams). After overwhelming the storage capacity of ferritin, free iron accumulates in the liver, pancreas, heart, and other organs, causing widespread damage.

Women are relatively protected from iron overload due to losses associated with menstruation and pregnancy. For example, in an average full-term pregnancy, the mother loses approximately 800 milligrams of iron. Thus, women typically manifest hemochromatosis later, most commonly after menopause.

The liver is usually the first organ affected, and hepatomegaly is the most common initial physical finding. Untreated, it can progress to cirrhosis, accompanied by portal hypertension and varices. Hepatocellular carcinoma occurs in approximately 30% of those who develop cirrhosis and is the most common cause of death in patients being treated for hemochromatosis.

Other common complications include cardiac dysrhythmias and congestive heart failure; diabetes mellitus from pancreatic involvement; hypogonadism and various hormonal deficiencies from testicular, pituitary and adrenal dysfunction; and arthritis – with the involvement of the second and third metacarpophalangeal joints (MCPs) a classic early finding. Excess iron also leads to increased susceptibility to infection from siderophilic bacteria, most commonly, Vibrio vulnificus, Listeria monocytogenes, and Yersinia enterocolitica.

Because many complications of hemochromatosis are not reversible, early diagnosis and treatment are critical for prevention. Features commonly reversed by treatment include fatigue, depression, abdominal discomfort, and bronze discoloration of the skin.

Screening assays for estimating total body iron stores are the serum iron level with percent transferrin saturation (serum iron divided by total iron-binding capacity), and the serum ferritin concentration. Every one microgram per liter increase in the serum ferritin concentration represents an increase of approximately five milligrams of iron stores.

Elevated ferritin alone is nonspecific, requiring a detailed history and physical with repeated lab studies to rule out other causes. With that in mind, if either the percent transferrin saturation or the serum ferritin concentration is elevated, genetic testing is recommended.

For those with results consistent with hemochromatosis, evaluation of the liver is critical to assess for the presence of cirrhosis. Over the past few years, improvements in lab studies, ultrasound, and magnetic resonance imaging (MRI) have significantly decreased the need for liver biopsy. For example, if the transaminase levels are normal, the serum ferritin is below approximately 1000 micrograms per liter, there is no hepatomegaly, and the patient does not drink excess alcohol, the risk of cirrhosis is extremely low. Also, MRI with T2* calculation is an accurate method for estimating hepatic iron content and has the advantage of being able to assess cardiac iron deposition. When there is a borderline case, or whenever there is doubt, liver biopsy remains the gold standard for diagnosing cirrhosis. 

Treatment of hemochromatosis involves removing the excess iron – via bleeding. Phlebotomy presents a very simple treatment in an age of increasing medical complexity, which is often a great relief to patients. This involves removing one pint (approximately 500 milliliters) of blood per session, which, depending on the patient’s hematocrit, contains between 200 to 250 grams of iron. Aside from treating the hemochromatosis patient, an advantage of phlebotomy is that the blood can be added to the donor pool (after standard blood screening).

Initially, phlebotomy is performed one to two times per week, as tolerated by the patient. It is then tapered to monthly, and then eventually to every few months, in order to maintain a ferritin level around 50 micrograms per liter or less. Since the average hemochromatosis patient has excess stores of about ten grams of iron, this represents approximately fifty phlebotomy sessions (not counting on-going iron absorption).꙳

For those with hemochromatosis, all adult first-degree relatives require genetic counseling and lab studies. In the case of children, testing the other parent usually suffices to determine their risk. If this is untenable, the child can wait until eighteen years of age to undergo genetic testing, given the time course of the disease.

For those who are asymptomatic and have no family history, the United States Preventative Health Task Force has come to no conclusions regarding screening. Arguments against screening involve the high costs of testing for a disease with variable penetrance (not everyone with the gene defect develops iron overload) and potential discrimination against patients by the insurance industry.

Given the high prevalence in those of northern European ancestry and the significant morbidity and mortality associated with untreated hemochromatosis, more experts are recommending at least targeted screening of late. They also recommend screening with genetic testing in order to detect those who have not yet developed iron overload, especially as these costs continue to decrease. Aside from these benefits, negative screening results are also helpful in relieving significant anxiety for patients and their families.

꙳ 1 ml RBCs = 1mg iron; a patient with a 40% hematocrit undergoing 500 ml phlebotomy loses 200 mg iron

References

Hemochromatosis, (2014), Retrieved from niddk.nih.gov/health-information/liver-disease/hemochromatosis (Accessed 03 October 2019).

Jameson, J.L., Fauci, A.S., et al, (Eds.)(2018). Harrison’s principles of internal medicine. 20th edition. New York: McGraw-Hill Education.

Kelley M, Joshi N, Xie Y, Borgaonker M. Iron overload is rare in patients homozygous for the H63D mutation. Can J Gastroenterol Hepatol. 2014;28(4):198-202.

Screening for hemochromatosis: recommendations from the U.S. preventive services task force. Ann Intern Med. 2006;145:I-18. doi: 10.7326/0003-4819-145-3-200608010-00002

Whitlock EP, Garlitz BA, Harris EL, et al. Screening for hereditary hemochromatosis: a systematic review for the U.S. preventive services task force. Ann Intern Med. 2006;145:209-23. doi: 10.7326/0003-4819-145-3-200608010-00009

Saddled With Siderosis Read More »

Volatile Vaping

/ Cases /

A 23-year-old man arrives by ambulance to the Emergency Department with severe shortness of breath, cough, nausea, and vomiting for several hours. Between rapid breaths and frequent coughing, he is able to state he has been healthy, has not traveled recently, and has had no recent ill contacts. He smoked one-half to one pack of cigarettes daily for a few years “on and off,” and began using electronic cigarettes (e-cigarettes) a few months ago on advice from a friend as a way to quit tobacco.

Exam – P 115, regular; R 28; BP 140/86; T 37.5⁰C; Pulse ox 86% saturation on 2L NC O2; Chest – tachypneic, with decreased breath sounds and scattered rhonchi bilaterally; Cardiac – tachycardic, without murmurs; Abdomen, Skin, Neuro – normal

Labs – WBC 15,000, neutrophil predominant, o/w normal CBC and normal chem panel; CXR – diffuse, bilateral, poorly-defined opacities

O2 saturation continued to drop, he became less responsive and required intubation and ICU admission.

Discussion

Although available for decades, e-cigarettes have recently been gaining in popularity. There are now over 500 brands and 10,000 flavors of e-cigarettes and growing. They are becoming more popular at a time when the United States has effectively banished tobacco from most public areas. Global sales exceed 25 billion dollars annually and are predicted to double over the next few years.

E-cigarettes are marketed as a safe alternative to tobacco, and many advertising campaigns promote their utility in smoking cessation. There are, however, very few high-quality and no long-term studies of e-cigarettes in smoking cessation. Also, many studies classify smokers who switch from tobacco to e-cigarettes as having quit smoking.

Unlike tobacco, e-cigarettes allow the user individualized control over variables such as temperature, wattage, amount of nicotine, the glycerin-to-propylene glycol ratio, and inhalational style (mouth-to-lung vs. deep-lung), providing a highly customizable experience. E-cigarette users have also been known to add tetrahydrocannabinol (THC), the high-inducing chemical found in marijuana, and cannabidiol (CBD) oil, a phytocannabinoid, to the e-cigarette liquid.

Especially attractive to younger people is an e-cigarette that looks like a USB flash drive, and a myriad of “kid-friendly” flavors, including mint, cherry, candy crush, cotton candy, strawberry-watermelon, and gummy bear.

The potential for harm from the components of e-cigarettes and the ingredients in the liquids is a growing concern. E-cigarettes contain a battery-operated element which heats a coil inside a wick saturated with liquid. The liquid is heated to approximately 200⁰C (up to 300⁰ C in temperature-control e-cigarettes). The main components of the liquid are propylene glycol and vegetable glycerin, both of which have been approved for oral ingestion but have not been studied as inhalational agents. Several studies have shown that a wide variety of chemicals are suspended in what is commonly referred to as a “vapor” (i.e. steam) but is actually an aerosol. These aerosols have been found to contain free radicals, heavy metals, formaldehyde, and many other volatile organic compounds.

Most e-cigarette liquids also contain nicotine, at levels set by the user. This allows for tapering doses, a common practice in nicotine replacement programs. Nicotine is widely known to be very addictive, and many studies have shown that adolescents are more vulnerable to this effect than adults. Chronic nicotine use in adolescents is also associated with a decreased ability to concentrate and increased stress levels.

The Centers for Disease Control and Prevention (CDC) reports from the 2015 National Youth Tobacco Survey that 27.1% of U.S. adolescents (approximately 7.3 million people) have ever tried e-cigarettes. This includes 37.7% of high school students and 13.5% of those in middle school. In 2018, the surgeon general deemed youth e-cigarette use to be an epidemic, and surveys show it continues to be on the rise. Many young people now start smoking with e-cigarettes. As with tobacco, nicotine dependence occurs rapidly and often becomes chronic. Surveys have shown many go on to smoke tobacco as well, some remaining dual users.

Recently, increasing numbers of e-cigarette-related lung injury have been observed throughout the United States. A CDC alert was published on August 23, 2019, reporting 193 cases of lung injury associated with e-cigarette use in 22 states between June 28th and August 20th of this year, including the first known death related to e-cigarettes on August 23rd. It is likely that these numbers are even greater and have been occurring over a longer period, as many cases were not linked to e-cigarette use at the time.

The mechanism(s) of lung damage in these cases is unknown. They involve a wide age-range and geographic distribution, and the pattern of lung injury is varied – including lipoid pneumonia, acute eosinophilic pneumonia, cryptogenic organizing pneumonia, and alveolar hemorrhage syndrome.

Studies of the effects of condensed e-cigarette aerosols on in-vitro human alveolar macrophages have shown dose-dependent toxicity. Below cytotoxic doses, increasing levels of reactive oxygen species (ROS) and inflammatory cytokines have been observed. These effects may be causing the inflammation and lung injury seen in these cases.

No link has been made to any specific product, ingredient, or infectious agent to date. One theory discussed on social media is that these cases are likely caused by CBD oil, given that the use of CBD is a more recent trend, and because it is an oil, unlike other e-cigarette liquids. Although there is no evidence to corroborate this theory, more research needs to be done. The CDC states it is continuing to work with state health departments in their investigations to find the source of this epidemic.

References

CDC, CDC, FDA, States Continue to Investigate Severe Pulmonary Disease Among People Who Use E-cigarettes, (2019), Retrieved from cdc.gov/media/releases/2019/s0821-cdc-fda-states-e-cigarettes.html (Accessed 26 August 2019).

CDC, Surgeon General’s Advisory on E-cigarette Use Among Youth, (2019), Retrieved from cdc.gov/tobacco/basic_information/e-cigarettes/surgeon-general-advisory/index.html (Accessed 26 August 2019).

Dinakar C, O’Connor GT. The health effects of electronic cigarettes. N Engl J Med 2016; 375: 1372-81. doi: 10.1056/NEJMra1502466

Scott A, Lugg ST, Aldredge K, et al. Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages. Thorax 2018; 73:1161-69.

Volatile Vaping Read More »

Palmar Paresthesias

/ Cases /

A 58-year-old right-handed man comes to primary care complaining of hand pain for several weeks. One month ago, he noticed tingling and burning pain on the palmar side of his right thumb, index and middle fingers. He works in an office and does computer work every day. His symptoms occasionally feel worse when he is typing. They fluctuate during the day and gets worse again overnight. One week ago, he noticed similar symptoms beginning in his left hand, but not to the same degree. His hands feel puffy and swollen, although he hasn’t noticed any physical changes.

He has had no history of neck complaints and notices no arm or hand symptoms with changes in head position. He does not have similar symptoms elsewhere. He is married, does not smoke, has one to two drinks several nights per week, and takes no medications. He has no significant past medical history and has not traveled recently. He is sedentary and states that although he had been moderately overweight for many years, he is frustrated by further weight gain over the past several months. His wedding ring and shoes have felt tighter over the past year but he attributes this to his weight gain.

Exam – P – 86, BP – 160/86, T – afebrile, Pulse ox – 98%, BMI – 29; large, coarse facial features, with skin thickening; normal sensory and motor evaluation of the upper extremities, including normal thumb strength, and no thenar atrophy; Tinel’s test (percussion over volar wrist) – negative bilaterally; Phalen’s test (wrists flexed to 90⁰ for one minute) + tingling sensation over the front side of his right thumb, index, and middle fingers; negative on the left

Labs – normal CBC, chemistries, except blood glucose (random)  – 168 mg/dL

Discussion

Carpal tunnel syndrome is the most common entrapment neuropathy, experienced by approximately five percent of the U.S. population. Although working on a computer is frequently cited as a common cause of carpal tunnel syndrome, a direct link has never been proven. Poor desk ergonomics may cause muscle strain associated with hand and wrist pain, however, these symptoms are not necessarily due to carpal tunnel syndrome. Most cases of carpal tunnel syndrome do not have an identifiable cause.

The carpal tunnel contains nine flexor tendons (two for each finger, one for the thumb) and the median nerve. It is formed by the carpals and the flexor retinaculum, a fibrous band located on the palmar side of the wrist, bound to the pisiform and hook of the hamate on the ulnar side, and the scaphoid and trapezium on the radial side. Increased pressure in the tunnel compresses the median nerve, causing injury. Additionally, inflammation of the flexor tendons in the carpal tunnel, either primarily, as in a repetitive motion injury, or secondarily, from the increased pressure itself, may cause further nerve damage.

Early symptoms include tingling and burning pain over the distribution of the median nerve in the hand, with sparing of the proximal palm and thenar eminence, as pictured.

The spared areas are innervated by the palmar cutaneous branch of the median nerve. This sensory branch arises proximal to the wrist and travels to the hand outside of the carpal tunnel. Thus, the sensory examination can help differentiate carpal tunnel syndrome from other causes.

Without treatment, median nerve injury can progress from sensory to motor symptoms, which may involve loss of hand coordination and overt weakness. Eventually, thenar atrophy may develop (except in those who have ulnar nerve contribution to the thenar area).

When the history and physical exam suggest carpal tunnel syndrome, nerve conduction studies (NCS) and electromyography (EMG) are often used as confirmatory tests. Positive findings on NCS include slowed median nerve velocities over the carpal tunnel, and EMG can detect denervation of hand muscles early, even prior to the patient noticing any motor symptoms. It can also help discriminate between muscle and nerve abnormalities.

Although the majority of cases have no known cause, carpal tunnel syndrome has been associated with several conditions. It is important to rule out a secondary cause, as many of these are life-threatening, and carpal tunnel syndrome may be the first sign of underlying disease. Some of the more common conditions include obesity, hypothyroidism, diabetes, arthritis, and pregnancy. Less common are hyperparathyroidism, renal failure and dialysis, sarcoidosis, amyloidosis, and leukemia.

This case provides an example of a rare condition causing carpal tunnel syndrome. The weight gain, tight-fitting shoes and wedding ring, coarsening of skin and facial features, increased blood pressure, and possibly the increased blood sugar (sample was not drawn while the patient was fasting) point to acromegaly, a condition of excess growth hormone in an adult. Acromegaly is most commonly caused by a pituitary adenoma (about 95% of cases) and further evaluation with additional laboratory studies and brain imaging are the next step in its evaluation. The appropriate treatment of acromegaly has been shown to reverse carpal tunnel syndrome (and many other associated signs and symptoms). The first physical changes associated with acromegaly can be very subtle, and the diagnosis is often delayed. When diagnosed and treated early, the life expectancy of those with acromegaly has been observed to be the same as that of the normal population.

If a cause of carpal tunnel syndrome is not discovered, treatment is determined by the severity of signs and symptoms. Early or mild carpal tunnel syndrome is usually treated with conservative measures: avoidance of repetitive motion, neutral wrist splinting, and nonsteroidal anti-inflammatories. A local steroid injection may also be used to reduce inflammation and swelling. If symptoms are severe or do not improve with conservative measures, a surgical referral may be required. In surgery, the flexor retinaculum is divided, by either an open or endoscopic method, providing an immediate reduction in pressure on the median nerve. Most patients will get significant relief after surgery. However, if the nerve was significantly damaged prior to surgery, recovery may take several months or longer. Physical therapy is usually advised to assist the patient with regaining full function.

References

Anderson, J.E. (1983). Grant’s atlas of anatomy(8th edition). Baltimore: Williams & Wilkins.

Jameson, J.L., Fauci, A.S., et al., (Eds.)(2018). Harrison’s principles of internal medicine(20th edition). New York: McGraw-Hill Education.

LeBlanc, K.E. and Cestia, W. Carpal Tunnel Syndrome. Am Fam Physician 2011; 83(8): 952-58.

Middleton, S.D. and Anakwe, R.E. Carpal Tunnel Syndrome. BMJ 2014; 349g6437. doi: 10.1136/bmj.g6437

Sevy, J.O. and Varacallo, M. Carpal Tunnel Syndrome, (2019), Retrieved from ncbi.nlm.nih.gov/books/NBK448179/ (Accessed 11 August 2019).

Palmar Paresthesias Read More »

Pyrexia In Pasadena

/ Cases /

A 33-year-old woman presents with complaints of fever, headache, and rash for the past several days. She lives in Los Angeles and works as a physician’s assistant (PA) in an Internal Medicine office. She often volunteers with a city outreach clinic, providing basic on-site medical care for homeless people. She has no significant past medical history, no recent travel outside Los Angeles, takes no medications, does not smoke or drink alcohol, and has been in a monogamous relationship for the past several years. She recalls no recent insect or tick bites, and aside from occasionally seeing rats at various outreach sites, she has had no contact with animals.

History of Present Illness – about five days ago she recalls developing a fever, with mild chills, malaise, and a headache, which was more intense behind her eyes. Because of her many ill contacts related to her work, she thought she was developing a cold or flu, and aside from taking oral hydration and an occasional Tylenol dose, she ignored her symptoms. One to two days later, she developed worsening fevers, increased retro-orbital headache, and diffuse muscle aches. This was soon followed by a rash, first over her abdomen, then on her arms and legs.

Exam – ill-appearing; T – 38.8⁰C; P – mild tachycardia; BP, RR, and O2 sat – normal; skin – erythematous, maculopapular rash over the abdomen, and extremities; no other focal finding or abnormalities

Labs – normal CBC, basic chemistries and U/A; rapid flu test – negative

Discussion

Acute febrile illness has a broad differential diagnosis, which requires close attention to the patient’s underlying health status (e.g. immune status, prior illness history), work and travel history, exposures, and other epidemiologic factors. Given this patient’s presentation and the fact that she resides in a subtropical region, consideration should be given to arthropod-borne viruses (arboviruses). The list of possibilities is extensive and is made even longer given that she works with a transient population, many of which have unknown medical and travel histories. The Los Angeles County Department of Public Health’s statistics show West Nile virus has been the most common arbovirus infection in Los Angeles County for the past few years. Some other arboviruses present in southern California include St. Louis encephalitis, Zika virus, dengue fever, chikungunya, and western equine encephalitis.

This case is also consistent with many other infectious etiologies, including leptospirosis, coccidioidomycosis, measles, EBV infection – and despite her reported sexual history, consideration should also be given to acute HIV, disseminated gonococcal infection, and secondary syphilis. Given the lack of nuchal rigidity and normal neurologic exam, meningococcal meningitis is less likely. Non-infectious etiologies, such as autoimmune disease (e.g. lupus), and neoplastic conditions are also possibilities.

This clinical picture, in a patient working on city streets, in proximity to rats, places a specific rickettsial disease near or at the top of the differential diagnosis. While tick-borne rickettsia such as Rocky Mountain spotted fever should be ruled out in this case, rickettsia carried by rat fleas is more likely, especially as there have been reports of increasing numbers of such cases in Los Angeles over the past several years.

Murine Typhus

Murine typhus, also known as endemic typhus or flea-borne typhus, is caused by Rickettsia typhi, a gram-negative, obligate, intracellular bacillus. Fleas ingest R. typhi while biting an infected animal (host), typically a rat or opossum. The bacterium is spread when the flea bites another host. The flea defecates while feeding, and the host will unwittingly scratch the infected feces into a pruritic flea bite wound. Human infections are incidental, as the main vector cycles are either rat-flea-rat or opossum-cat flea-opossum.

flea – scanning EM

The incubation period for murine typhus is one to two weeks. The most common symptoms are fever, headaches, and malaise. The “classic triad” of fever, headache, and rash only occurs in about one-third of cases. Severe complications include meningitis, focal neurologic changes, respiratory failure, acute renal failure, and septic shock. The majority of cases, however, are relatively mild, and the case fatality rate, even without antibiotic therapy, is low. Increased mortality is associated with older age and immune compromise.

Given the clinical overlap observed among rickettsial diseases, PCR and/or indirect immunofluorescence assays (IFA) can be done to discriminate between them (and other etiologies). Prior to the return of specific diagnostic lab assays, empiric antibiotic therapy includes doxycycline due to its effectiveness against rickettsial infections.

References

CDC, Flea-borne (murine typhus), (2019), Retrieved from https://www.cdc.gov/typhus/murine/ (Accessed 07 August 2019).

Chu, J.T., Hossain, R., et al. Case 22-2017 – A 21-year-old Woman with Fever, Headache, and Myalgias. N Engl J Med 2017; 377:268-78. doi: 10.1056/NEJMcpc1616399

Flea-Borne (Endemic) Typhus, (2019), Retrieved from www.publichealth.lacounty.gov/acd/VectorTyphus.htm (Accessed 07 August 2019).

Stern, R.M., Luskin, M.R., et al. A Headache of a Diagnosis. N Engl J Med 2018; 379:475-79. doi: 10.1056/NEJMcps1803584

West Nile Virus and Other Arbovirus Diseases: 2017 Los Angeles County Epidemiology Final Report May 1st, 2018, (2018), Retrieved from publichealth.lacounty.gov/acd/docs/Arbo2017.pdf (Accessed 07 August 2019).

West Nile Virus Testing, (2019), Retrieved from www.publichealth.lacounty.gov/lab/wnv.htm (Accessed 07 August 2019).

Pyrexia In Pasadena Read More »

Fever in Florida

/ Cases /

A 42 year-old man presents with acute onset fever and chills, with headache, intermittent abdominal pain, and very severe pain in his wrists, ankles, and low back for the past two days. He has no significant past medical history; he lives in Florida and works as an electrician. He has had no recent travel, no recent sexual contacts, and takes no medications. Aside from an occasional mosquito bite, he recalls no significant insect or other animal exposure, recent ill contacts, and has had no known tick bites.

Exam – temperature: 39.0 C, mild tachycardia, ill-appearing, but otherwise without focal findings, including no rashes, joint effusions, and no neurologic findings

Labs – normal CBC and basic chemistry panel, except for mild lymphocytopenia

Discussion

Acute febrile illness challenges clinicians with a very broad differential diagnosis – infectious diseases, collagen vascular diseases, endocrine disorders, to name just a few categories. When fever is associated with hemodynamic stability and generally normal physical findings and initial labs, it is typically attributed to a “viral syndrome” and managed with supportive care and outpatient monitoring. This patient, however, resides in a subtropical region and is showing symptoms and findings which would place a specific emerging vector-borne threat at the top of the differential diagnosis.

Aedes mosquito

Chikungunya

Chikungunya virus is an arthropod-borne single-stranded RNA virus (arbovirus), spread via Aedes mosquitoes, mainly Aedes aegypti and Aedes albopictus.

Aedes distribution (blue)

Chikungunya attack rates are very high, with WHO reports as high as 45% in some areas. Endemic to Africa, it spread to the Americas, mainly to the Caribbean, during the 1980s. It is typically spread by travelers, with thousands of documented cases imported to the United States from the Caribbean in 2013 and 2014. There have now been several cases of locally-acquired chikungunya infections (autochthonous) reported in the past few years throughout Florida and most other southern states. Given that the distribution of Aedes mosquitoes includes all of the southern United States, this trend is likely to increase, reinforcing the need to institute excellent vector control programs.

The incubation period for chikungunya infection is two to ten days (most commonly three days) and presents with sudden-onset severe fever, headache, and joint pains. A pruritic maculopapular rash has been observed with variable frequency in several different studies. Fever and other symptoms defervesce over seven to ten days, however, the arthralgias may persist for weeks to months, and in some cases, years.

If the patient presents early in the course of chikungunya infection, as in this case, diagnosis may require viral PCR testing as the IgM antibody response becomes detectable several days to one week after the onset of symptoms. If PCR is unavailable, the patient can be monitored closely to follow the antibody response, first with IgM, and then IgG antibodies.

Treatment of chikungunya is supportive, as there is no specific antiviral medication available. Given that chikungunya and dengue viruses both have the same vector and overlapping clinical features, dengue virus infection needs to be ruled out, especially since dengue fever has a significantly higher case-fatality rate. Until dengue is ruled out, aspirin and non-steroidal anti-inflammatory medications should be avoided, so as not to increase the risk of hemorrhage.

Vector control remains of paramount importance in the prevention not only of chikungunya virus, but of all other known viruses carried by Aedes mosquitoes, including dengue fever, yellow fever, zika, West Nile fever, eastern equine encephalitis, western equine encephalitis, Mayaro fever, Venezuelan equine encephalitis, Japanese encephalitis, and others!

References

CDC (2018), Chikungunya virus, Retrieved from https://www.cdc.gov/chikungunya (Accessed 02 August 2019).

Jameson, J.L., Fauci, A.S., et al, (Eds.)(2018). Harrison’s principles of internal medicine. 20th edition. New York: McGraw-Hill Education.

Thwaites, G.E., Day, N. Approach to fever in the returning traveler. N Engl J Med 2017; 376: 548-560. doi: 10.1056/NEJMra1508435

Weaver, S.C., Lecuit, M. Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med 2015; 372:1231-1239. doi: 10.1056/NEJMra1406035

Fever in Florida Read More »