Sore Throat (lasting over 4 days) — Full Text

During the pandemic, if we hear “sore throat” that’s been going on less than 10 days, we think “Covid”.  Every office & clinic has its own way of testing for it, & won’t let the patient inside.  One Covid-Negative test isn’t 100%, although a second negative 2 days later would be.  Unfortunately, every site that does Covid tests has different turn-around times; sometimes results are back in 30 minutes, others may take a week!

Here we discuss conditions in the second column below. See also Sore Throat 1-3 Days — Full Text.

Causes of Sore Throat (Pharyngitis)

xxxxxMost Common Causes
Common Simple Viruses
Strep Throat

xxxxxxWe Send to E.R. (very rare)
Peritonsillar Abscess *
Deep Tissue Infection **
Diphtheria **
Neutropenia **
Tularemia **
Rabies **

xxxxxWe Should Never Forget
Acute (Primary) HIV
*  Life-threatening, & uncommon
**  Life-threatening & very rare
Covid-19 [only if ill less than 10 days]
Strep Throat [unlikely after 3 days]
Acute (Primary) HIV
Herpes simplex ?
Syphilis (secondary stage)
Don’t Miss These” (see 1st Column)
xxxxxxxLong-Standing Duration
Allergic Rhinopharyngitis (“allergies”)
Gastroesophageal Reflux (GERD)


Once a Sore Throat has persisted at least 4 days, without any typical symptoms of a common cold, and Covid testing is negative, we can eliminate a “simple virus” as the cause.  We can probably drop Strep also, which almost always resolves on its own by then.  Still, we do usually obtain a Rapid Test, not so much because Strep is likely, but it’d be embarrassing to engage in any further work-up without it.

We obviously remain alert to “Don’t Miss” conditions.  But let’s say our patient is certainly not that ill, and let’s say we’ve ruled out Covid-19.  The extent to which we order other laboratory tests depends on the clinical scenario, & on patient risk factors.  Let’s cover them.

**  Mononucleosis  (“Mono”)  —  This is quite common among teens & young adults; little kids with Mono tend not to have symptoms, & older persons are already immune.  It’s caused by Epstein-Barr Virus.

We suspect Mono when fatigue is prominent.  We especially tune in to it if there are tender lymph nodes in unusual locations (behind the ear, back of head, armpit, or inner elbow).  If we find an enlarged spleen when we examine the abdomen, we’ve virtually clinched the diagnosis.

Unfortunately, the common “Monospot” (“Heterophile”) blood test for diagnosis is often false-negative in early illness.  It sometimes takes 3 or 4 weeks to show up.  There’s a better, more expensive, “Epstein-Barr IgM Antibody,” though sometimes it too may be negative, requiring other (even more expensive) antibody tests.

The best tests to clue us in early on include:

  • A Complete Blood Count (CBC), with a manual differential (the lab tech actually looks under the microscope for “atypical lymphocytes”)
  • Liver Function Tests (for liver enzymes ALT & AST).  Mono affects the liver, & these tests get high with any liver disease.  If normal, the odds are way against Mono, though if elevated they don’t prove it
  • For sure-fire diagnosis: prescribe Amoxicillin, which causes a generalized, non-itchy, splotchy red rash maybe 100% of the time [we don’t actually do this].

When it clinically seems like Mono, but the Monospot is negative, and the patient is not very ill, we can usually make a tentative diagnosis & repeat weekly Monospots.  But I’ve seen a few clinicians fret & sweat when working up, not “sore throat,” but rather an enlarged lymph node.  That’s because cancer (lymphoma) is a possibility.  That’s the time to order Epstein-Barr Virus & all other antibody tests (depending on lab turnaround time).

There’s no treatment for Mono; it gets better on its own (there are very rare complications).  The main danger is a ruptured spleen, so patients should avoid contact sports (including vigorous sex) & motorcycle accidents.  It’s also good to avoid alcohol (Mono is a liver disease).

And of course, any time we think “Mono,” we also need to think (and address) possible Acute (Primary) HIV [see right below], which looks the same symptom-wise (but is obviously different).  Actually, Acute HIV can cause false-positive Monospot tests.

**  Acute (Primary) HIV  —  a.k.a. “Acute Retroviral Syndrome,” “Primary HIV.”  Incubation period from the moment of transmission to beginning of symptoms is 9-30 days.  Symptoms last 1-3 weeks.

Initial studies found that around 50% of newly-infected persons experience a range of symptoms:

  • Fever, Fatigue, Generalized Swollen Glands (lymph nodes)  —  most common
  • Sore Throat, Rash, Achy Joints / Muscles, Headache  —  common
  • Diarrhea, Oral/Genital Ulcers, Nausea/Vomiting  —  much less common

Subsequent studies suggest that if we inquire extensively, up to 80% of HIV-positive persons recall some sort of minor illness around the time of likely transmission.  So many people may hardly feel any symptoms at all.

This is the “Window Period,” when a test for HIV-Antibody are negative.  It turns positive at approximately:

  • 1 month —  50% of persons; 3 months  —  95%; 6 months  —  >99%
  • The “4th Generation” HIV blood test may show up 18 days from infection.  This includes antibody and an antigen, and is what almost all commercial labs use now.  But over-the-counter “do-it-at-home tests” are simply antibody.

The diagnosis of Primary HIV is best made by “Viral Load” testing for “HIV-1 RNA by PCR.”  This test counts the number of HIV-virus particles.  During Acute HIV infection, before the body can make antibodies, an enormous amount of virus circulates in blood.  The viral load may approach 1,000,000 (the average viral load in untreated HIV is around 20,000).  Low levels suggest long-standing infection, or (if antibody test remains negative) laboratory error.

But Viral Load tests are expensive ($100 – $200); we can’t order them on everyone with a sore throat.  The presence of risk factors is helpful, but some patients won’t tell us.  If you have risk factors for HIV (esp. unprotected anal sex with a man, or unsafe drug injection), and get a sore throat that lasts at least 4-5 days, be honest with your clinician.  There are various advantages to diagnosing HIV early:

  • Acute HIV is very contagious (avoid sex for 4 months)
  • Early treatment may preserve health in the long run
  • Early treatment prevents contagion, usually within 1-2 months
  • Acute HIV is the best time to test for drug resistance (even if you don’t plan on starting medication just yet)

See disease link Acute HIV.

**  Gonorrhea  —  Caused by performing oral sex on a man (regardless of your own gender).  You can’t get this from performing it on women, because the bacteria has to be deposited back in the throat.  Pharyngeal Gonorrhea (“pharynx” = “throat”) feels like any other sore throat — bad, mild, or very often completely asymptomatic.  Physical examination isn’t useful, since the throat can look anywhere between horrid & normal.

Gonorrhea isn’t detected by a regular throat culture; it needs a special swab.  If you have a sore throat & think you’re at risk, tell your medical provider.  It’s not extremely dangerous, but certainly worth treating, especially since Gonorrhea in the throat can become resistant to antibiotics you might not even be taking (by picking up resistance genes from other oral bacteria).

(**  Chlamydia)  —  We can find this STD in the throat of people who perform oral sex on men, and when we do, we routinely treat it.  However, it may be debatable that the STD Chlamydia trachomatis can cause disease in the throat.

**  Herpes Simplex Virus (HSV)  —  HSV causes a mouth infection (stomatitis), but can also cause a sore throat (pharyngitis).  HSV Type-1 is usually acquired in childhood, then recurs in periodic outbreaks of cold sores on the lip.  HSV Type-2 is almost always transmitted sexually, & might occur in the throat after oral sex (though usually affects the mouth).

If you get a bad sore throat 2-12 days after performing oral sex, ask your examiner if they see blisters.  If so, it’d be worth a test for HSV (by testing the blisters, not a blood test).  Also ask about blisters if you get recurrent sore throats, which might be outbreaks [with the initial infection having occurred anytime in the past).  For recurrent outbreaks, the HSV test may be false-negative unless done in the first 1-2 days.

**  Syphilis  —  Secondary syphilis can definitely cause pharyngitis.  However, there are invariably other findings too, such as fever, swollen glands all over (lymph nodes), rash (check especially the palms & soles), condylomata lata (moist gray plaques on mucus membranes), & lots more.  Indeed, pharyngitis as the only manifestation of secondary syphilis is so unlikely that I no longer look for the disease in such cases.  Symptoms of secondary syphilis begin more than 2 months after contracting the bacteria.  See the link for a deeper discussion on the disease and its stages.

**  Low White Blood Cells (Neutropenia)  —  If the body stops producing Neutrophils (the most common kind of white blood cells), due to a rare medication reaction, cancer, or other obscure disease, there’s high risk of getting an overwhelming bacterial infection.  The first signs of neutropenia (low neutrophil count) are fever and/or blisters in the mouth & throat.  The diagnosis is simple with a Complete Blood Count (CBC).

**  Tularemia  —  A disease of poor countries, caused by contaminated food or water.  Mouth and throat pain are severe, oral blisters are prominent.  In the US, tularemia would only occur in the throat if you pulled a tick off your skin, & then happened to lick your fingers.  Diagnosis is hard; blood tests take a while.  Two or more cases together get reported as possible bio-terrorism [it’s that rare].

**  Rabies (early)  —  Just to be complete; a fair number of the rare patients with human rabies seek care for “sore throat” (& are invariably prescribed penicillin).  In its early stage, the only clue might be agitation at sight of water (hydrophobia), or when a whiff of air is fanned across the face (aerophobia).  Risk would include wild animal bite, being licked by a dog or cat in a poor country, or any contact with a bat.  There’ve been around 50 cases in the US since 1990.

NOTE — Since bat bites aren’t felt or noticed, the CDC recommends rabies vaccination if you awaken from sleep & see a bat in room (or if bat is found in a room with a child or mentally-incompetent adult [including anyone stoned on anything]).

How We Manage Sore Throat Lasting Over 4 or 5 Days

When a patient’s sore throat has lasted this long, without having developed an obvious cold, we obtain:

  • Strep throat screen, of one form or another, if not yet done (for Strep).
  • Complete Blood Count (CBC) (for atypical lymphocytes suggesting Mono; also finds Neutropenia)
  • Monospot blood test for Mono (may be false-negative for 2-3 weeks)
  • Liver Function Tests (LFTs)  (looking for slight elevation of ALT or AST, suggesting Mono)
  • Maybe a throat swab for Gonorrhea, if there’s a history of very recent oral sex on a new male partner (different from Strep swab)
  • Review risks for Acute HIV (order a Viral Load if significant risks)

The CBC & LFTs are almost always abnormal with Mono.  A positive Monospot clinches the diagnosis, but is often false-negative the first 2 weeks.

If the CBC / Liver Tests are suggestive, we make a tentative diagnosis of Mono.  But it’s absolutely necessary to inquire well about risk-factors for HIV infection within the past 9-30 days.  If the latter is worrisome, we strongly consider ordering both a routine HIV test and also an HIV-1 Viral Load.  Acute HIV resembles Mono in virtually all aspects (& there are reports of false-positive Monospots in Acute HIV).

When the Monospot is negative, but patient remains symptomatic, especially in terms of fatigue, and just not feeling well, we keep repeating the test weekly.  If the patient feels pretty ill, we order more accurate tests for various Epstein-Barr Antibodies.  Clinicians may order those right away if a patient has insurance.

TRUE STORY:  A college student went to a local “clinic” for “sore throat.”  They did lots of tests, the bill was $825, & her insurance wouldn’t pay because it wasn’t a true “urgent care” clinic.  Fortunately, she was pretty assertive, argued, & they eventually covered it.  But, beware [$800 !!! — pretty expensive sore throat].

Of course, other common viruses can produce a mononucleosis-like illness, so the Monospot may always remain negative, as will all Epstein-Barr tests.  If the Monospot is positive, that’s all there is to it… almost.  There are reports of false-positive tests during Acute HIV [see above].

With all these viral infections, the sore throat fades and patients mainly complain of fatigue.  But what they don’t feel that way; they only have is a nagging sore throat, that goes on and on (even months).  Though there’s no good data, I offer one of the following treatments (both to make the patient feel better, & also help diagnose what’s causing their symptom):

I treat for 1-2 weeks, with highest doses of all possible drugs.  That’s because we’re seeking a Diagnosis; if we give low doses, & nothing happens, we won’t know if it’s wrong diagnosis or too-little-medication.  If treatment helps, I continue it at a more standard dose.  If symptoms remain unchanged, I go for the other treatment above.

If that’s no help either, I explore mood symptoms, and treat as such if Anxiety or Depression appear plausible.  Eventually, I may bail out and refer to an Ear-Nose-Throat (ENT) specialist, but that’s only happened to me  once in the last 25 years [for pure “sore throat” without other symptoms].

Enough said.

See also Sore Throat for the clinician’s condensed thought-process when face-to-face with a patient.

For Sore Throat going on 3 Days or Less, see that topic’s Full Text.

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