​Kembara Xtra - Medicine - Rocky Mountain Spotted Fever

​Kembara Xtra - Medicine - Rocky Mountain Spotted Fever 
The most prevalent form of spotted fever rickettsiosis (SFR) in North America is called Rocky Mountain spotted fever (RMSF). Of all reportable rickettsial infections in the US, it is linked to the greatest incidence of severe and fatal consequences.
The bacteria Rickettsia rickettsii is the cause of RMSF, a systemic small and medium vessel vasculitis spread by ticks. Starts in the wrists and ankles and spreads to the palms, soles, and trunk; symptoms include fever, headache, and myalgia as well as cardiovascular, musculoskeletal, cutaneous, central nervous system (CNS), renal, hepatic, and pulmonary system(s) impacted

Epidemiology 

Ticks serve as both primary reservoirs and vectors in the United States. The Rocky Mountain wood tick, Dermacentor andersoni, is found in the western United States, the American dog tick, Dermacentor variabilis, is found in the eastern two-thirds of the country, and the brown dog tick, Rhipicephalus sanguineus, is found in every state.



Incidence

The annual incidence of SFR in the United States grew from 1.7 cases per million people in 2000 to 13.2 in 2016. All states, with the exception of Alaska and Hawaii, have reported cases. Over 50% of SFR instances occur in Arkansas, Missouri, North Carolina, Tennessee, and Virginia; RMSF is also detected in Canada, Mexico, and all of Central and South America. In Arizona, cases that hadn't previously been found there have also been found.
Cases happen all year long. The peak months for outdoor activities are May through August, when most cases are documented. The highest incidence occurs in people between the ages of 60 and 64. Children under the age of 10 had the highest recorded death rate.
Prevalence
4,470 instances were reported in the USA in 2012.
Only 0.1% of ticks are carriers of dangerous rickettsial species.

Pathophysiology and Etiology 

After 6 to 10 hours of eating, a mature tick discharges R. rickettsii from its salivary glands. Pathogens infect vascular endothelial cells, resulting in small and medium artery damage throughout the body and disseminated inflammation. Vascular permeability later on can result in cerebral and pulmonary edema.
Platelet ingestion locally causes a distinctive petechial rash. Meningoencephalitis, ARF, acute respiratory distress syndrome, shock, arrhythmia, and seizures can also be brought on by subsequent end-organ injury. Symptoms start to show up 3 to 12 days after the bite or between 4 and 8 days after the tick was found attached. R. rickettsii may cross the placenta and infect the fetus, however this is uncertain.
Rarely, direct tick blood injection into open wounds or conjunctivae might result in RMSF.

Risk factors include exposure to the outdoors frequently or living in wooded regions; coming into contact with outdoor pets or wild animals; and having a tick that has been engorged or present for more than 20 hours.


Basic Prevention 
Wear light-colored clothing, long sleeves, pants, socks, and closed-toe shoes to minimize tick exposure; tall grasses, open regions with low bushy vegetation, and woodland areas have the highest tick exposure. Use insect repellents with DEET.
 Spraying permethrin on garments
.Regular tick checks, timely and correct tick removal, and never touch ticks with bare hands.
Following tick removal, wash hands and the bite site with soap and water to prevent the possibility of mucosal inoculation.


Diagnoses
Regardless of a prior history of tick exposure, have a high index of suspicion for rickettsial infections in patients who present with "flu-like" symptoms in the summer.
Delaying empirical therapy raises the risk of mortality and long-term consequences.

History 

Consider RMSF if you experience an acute febrile fever and rash, especially if you have traveled to an endemic location or engaged in outdoor activities during the late spring or summer and have a history of possible tick exposure within the previous 14 days. 30% to 50% of the time, a tick bite goes unnoticed.
 Usually begins with sudden development of fever, severe frontal headache, malaise, myalgia, anorexia, nausea, vomiting, and photophobia within the first 1 to 4 days, mimicking a viral infection.
Rash often develops 2 to 4 days after the start of a fever; it first shows as small, pink macules that blanch before spreading to the trunk, where it may take on a maculopapular appearance.
 Palm and sole involvement, which typically appears by the fifth or sixth day, is accompanied by a widespread petechial rash and is a symptom of severe disease. Rash typically spares the face. Even while children under 15 years old have rashes more commonly (>90%), only around 60% of children with RMSF have the traditional triad of fever, rash, and tick bite. 10% of patients never experience a rash, hence the appearance of a rash should not be the deciding factor in treatment.
Conjunctival injection, mental status changes, restlessness, arthralgia, peripheral or periorbital edema, leg discomfort, and hearing loss are further symptoms.


Clinical evaluation 
The normal rash begins as an erythematous, macular, or maculopapular exanthema (1 to 5 mm in diameter); 50% progress to petechial or purpuric lesions. The typical fever is >102°F.
On dark skin, the rash may be difficult to see. In severe cases, the rash may cover the entire body, including the mucous membranes, and it may develop into necrotic or gangrenous lesions.
The rash is not accompanied by urticaria or pruritus.
AMS, lymphadenopathy, hepatosplenomegaly, generalized right upper quadrant discomfort, and edema on the palms or soles of the feet

Differential diagnoses include: Meningoencephalitis, meningococcemia, upper respiratory infections, urinary tract infections, TTP/ITP, idiopathic vasculitides, toxic shock syndrome, viral gastroenteritis, mononucleosis, and viral gastroenteritis.
 Drug reaction or serum sickness Kawasaki illness, infective endocarditis, ehrlichiosis, Lyme disease, babesiosis, boutonneuse fever, leptospirosis, and other tick-borne ailments are also the differential diagnosis. 

Laboratory Results 

IgM and IgG serologic responses to R. rickettsii, along with a high degree of clinical suspicion, are used to diagnosis the majority of cases with RMSF. Don't put off therapy in anticipation of a cure.

Initial Exams (Lab, Imaging) 
The gold standard in serology is indirect fluorescent antibody (IFA) testing, which is used for specific laboratory diagnoses.
- IFA is 94-100 percent sensitive 2 weeks after the start of the illness, but it cannot tell R. rickettsii from other spotted fever-group rickettsii.
- It is impossible to distinguish between a single increased IgG titer linked to an acute sickness and earlier infections because of seroprevalence.
- It is possible to demonstrate growing IgG or IgM antibody levels by analyzing two serum or plasma samples in succession, which is necessary to confirm an acute infection.
- Typically, these samples need to be collected at least two to three weeks apart in order to check for an antibody titer increase of fourfolds or more to confirm the diagnosis.
- The best window for testing is 14 to 21 days after the onset of symptoms.
 Unspecific laboratory examinations
- Variable, frequently normal WBC count
60% of children had platelet thrombocytopenia (150,000 cells/L), and 50% of patients have hyponatremia (135 mEq/dL) and increased hepatic transaminases.
- Additional symptoms include anemia, a rise in blood urea nitrogen/creatinine, PT/PTT, hyperbilirubinemia, and hypoalbuminemia.
- Mononuclear pleocytosis, increased protein, and normal glucose may be seen in CSF.
Imaging techniques are rarely beneficial.

Other/Diagnostic Procedures
A 3-mm punch biopsy can be used to produce a quick direct fluorescent antibody (DFA) test with a sensitivity of 70% and a specificity of 100%.
A novel method for diagnosing suspected rickettsial infections during the acute stage of sickness is rickettsial DNA detection utilizing PCR of skin biopsy samples.
Enzyme-linked immunosorbent assay (qualitative)
Interpretation of Tests
Concurrently test serum from the acute and convalescent phases.
Early therapy may prevent the production of antibodies.
In endemic areas, seropositivity rises with age.
The presence of a positive spotted fever group Rickettsia antibody does not always indicate an acute infection.

First-line management medication

For both adults and children, doxycycline is the drug of choice.
Without prompt antibiotic treatment, rickettsial infections have a high rate of morbidity and mortality (20–30%). Other antibiotics have significantly lower efficacy.
Doxycycline 100 mg PO or IV every 12 hours until 3 days after the fever goes away in adults and children over the age of 18 who weigh more than 45 kg.
Children under 45 kg: Doxycycline 2.2 mg/kg PO or IV every 12 hours till 3 days after the fever goes away.
In cases of pregnancy, the first-line treatment is Doxycycline 100 mg PO or IV every 12 hours until 3 days after the fever has subsided. The second-line treatment is chloramphenicol 50 to 75 mg/kg IV divided into 4 doses every day for 7 days. Despite its paucity, the available research indicates that there is no elevated risk of teratogenicity.
Fever normally goes down within 24 to 48 hours with early treatment; longer if patient is extremely unwell. Total course of treatment is typically 5 to 7 days, at a minimum, and may be longer if severe or complicated condition. If the patient is promptly treated and doesn't respond to doxycycline within 48 hours, think about a different diagnosis.
There is no evidence of RMSF doxycycline resistance.
 Negative outcomes could include the following:
- dyspepsia. With food and water, take your medication. Avoid dairy, iron, and antacids as these may inhibit the absorption of medications.
- There could be photosensitivity. Use sunscreen and limit your exposure to the sun.
- Children under the age of 8 have no risk of dental discoloration.
Doxycycline is contraindicated in cases of severe allergy; in cases of life-threatening illness, fast desensitization may be an option.
Next Line
The alternate treatment for RMSF is chloramphenicol, which has unfavorable hematologic consequences (such as aplastic anemia) and a higher case death rate. 

Pregnant women's issues

Despite the potential danger to fetal bones or teeth, along with maternal hepatotoxicity and pancreatitis, doxycycline is recommended for this life-threatening illness in pregnancy if suspicion is high.
Chloramphenicol may be considered, but it should be avoided in the third trimester due to the risk for gray baby syndrome. Short-term doxycycline is safe with nursing.

Referral 
If a patient has a severe doxycycline allergy, consider having them contact an immunologist or allergist in addition to an infectious disease specialist.
 Inform public health authorities about any incidences of RMSF.

Further Treatments 

Patients who have suffered neurologic injury could need extensive physical and cognitive therapy.

The nedd for oral antibiotic medication for nausea/vomiting prevention and CNS dysfunction are the admission requirements.
- Patients with immune system compromise - particular acute organ failure,
failure of oral pain medication  and shock patients are also reasons for admission into the ICU. 


Discharge requirements - Fever resolution - Capability to take oral medication and nourishment


Follow-up If close follow-up is possible, patients with mild disease may be treated as outpatients.
Patients with moderate to severe illness should be hospitalized.
Immunity against infection does not last a lifetime.
patient observation
 Until symptoms go away, check on patients receiving outpatient care every 2 to 3 days.
 If clinically necessary, repeat CBC, electrolytes, and LFTs
DIET
If intake is inadequate, think about supplemental nourishment.

Modification of Lifestyle 

General precautions and prevention for tick avoidance while outdoors in endemic areas


Prognosis Timely administration of the right antibiotics has a significant impact on prognosis.
If treatment is delayed until the fifth day of illness, death may increase by three times.
The prognosis is excellent with symptom relief and no sequelae when treated quickly.
Children under the age of 10 and people over the age of 70 have a higher risk of morbidity and/or fatality, while patients with G6PD deficiency have a higher chance of developing fulminant RMSF, which can be fatal in as little as five days.

Complications include: seizures, a focal neurologic deficit, encephalopathy, most usually characterized by a temporary impairment of level of consciousness, and acute renal failure due to renal damage.
Hepatitis, respiratory failure, and congestive heart failure (CHF)
Additionally possible symptoms include proximal muscular weakness, personality changes, paresthesias, deafness, secondary thromboses, and tissue necrosis.

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