Itchy Immunology

‘Ugh, my wrist itches’ my mom complains after our third night in our Airbnb in Trastevere, Rome. A seemingly harmless comment, considering mosquito season is right around the corner, and, arguably, many other physical complaints would be worse to encounter while on holiday. However, as a student living in a 15-person student house in the student-filled city of Utrecht, itching has become a trigger word that sparks a feeling that I can best describe as panic.

The Itch of ‘23

In the winter of 2023, no one was safe. Every other week, someone’s boyfriend, girlfriend, girlfriend’s roommate, or a friend of a girlfriend’s roommate encountered the itch. And for us, when someone in your direct environment encountered the itch, it meant:

1. Filling your 12m2 room with garbage bags stuffed with the clothes you wore for the past 3 days and keeping them sealed for 3 days (or 5, just to be safe?).

2. Changing your bedsheets, washing them at 60 (or even better; 90?) degrees Celsius while fighting with your roommate over who could use the shared washing machine first.

3. Running to the pharmacy and spending 30 euros on a small tube of cream that you must rub over your entire body and asking the roommate that you’ve known for only 2 months if they can help you with your back.

4. Going to sleep in your newly cleaned bed while covered with the cream.

5. Rinsing off the cream after 12 hours and repeating step 2.

6. Keeping track of the clothes you wear for the next days, putting them in separate garbage bags, making sure to keep them sealed for 3 days (or for the whole week, just to be sure?).

7. Waiting for 7 days and then repeating steps 2-6.

And then… you wait…

For 6 weeks, because after that you’re in the clear for developing the itch. At least until you get the next warning, because your roommates’ boyfriends’ roommate came over and maybe sat on your couch.

If this sounds like a disproportionate amount of work to prevent developing something as simple as an itch, it might help to mention that the specific itch I’m referring to is the one caused by scabies mites (scientific name: Sarcoptes scabiei). Scabies mites are microscopic parasites that dig into your skin and hang out there. Yikes. The main symptom of a scabies infection is an intense, all-consuming itch that typically worsens at night, making it difficult to sleep – which has a huge influence on people’s wellbeing. In addition, as scabies typically spreads between people via skin-on-skin contact, the infection quickly gained a ‘taboo’ status in the student population, similar to that of sexually transmitted infections. However, scabies mites can live outside of the body for up to 3 days, which means skin-on-skin contact is not required to contract scabies. In fact, scabies can also spread via shared bed linen, towels, couches, or clothes. This is one of the reasons the itch of ’23 spread so quickly between students - sharing a couch with 15 people is rule rather than an exception in Dutch student houses.

The immunology of itching

Though the idea of tiny spider-like creatures crawling inside your skin might automatically make you itchy, at the height of a typical scabies infection, a person is infected with only 10 to 15 mites. So, how can such a small number of these microscopic animals cause such an intense itch?

Skin contains multiple types of nerve cells that can sense different stimuli – think of pain, temperature or pressure. The nerve cells that are sensitive to itch are called pruriceptors. When these cells are stimulated, they send a signal to the brain saying, “scratch here”. Stimulating these cells sends a signal to the brain, that subsequently induces the urge to scratch the stimulated area. These itch-sensitive nerve cells can be activated via many ways, and part of the itch during scabies infection is caused by the direct triggering of these cells by the scabies mites. For example, certain proteins in Scabies mite feces can directly bind pruriceptors. However, a big part of the itch during a scabies infection is caused by a player that is closer to home: your own immune system.

Scabies – ancient parasite with modern consequences

For the majority of the Dutch population, scabies was a new phenomenon during the outbreak a few years ago. However, scabies has actually been around for a long time.

It is referred to multiple times in the Bible and it marks one of the first human diseases for which we definitively pinpointed a cause. In other words, people understood pretty early on that it was these microscopic mites causing this type of intense itching.

As scabies has been around for such a long time, the mites have had quite some time to develop tricks to manipulate their host and make their life in the skin a bit easier. This has resulted in an elaborate dance between the mites and the human immune system. At the start of the infection, the mites try to block the human immune system, hoping stay in the skin unnoticed so they can set up shop. When you haven’t had a scabies infection before, the mites can be quite successful in this. With a first-time infection, people typically don’t show any symptoms for multiple weeks despite being infected by mites.

However, at some point, the immune system manages to catch up and starts to respond to the mites. This immune response produces all kinds of mediators that can directly – or indirectly – interact with pruriceptors. One way that this happens is via the activation of a specific type of immune cell called mast cells. Mast cells are filled to the brim with infection-fighting molecules. When they are activated, mast cells spit out these molecules to cause an inflammatory response, which can be very handy when your body wants to fight off an infection. However, some of the molecules released by mast cells can also directly stimulate pruriceptors, worsening the itch response.

It's good to know that mast cells aren’t the whole story behind the itch. Next to mast cells, scientists think that many other immune cells and mediators might intensify the itch response. For most of these cells and mediators, the precise way they cause or worsen the itch during a scabies infection is still under investigation.

Treating scabies

Luckily, we can treat scabies very effectively: either with permethrin (the active component of the beloved abovementioned cream) or ivermectin (the active component of the anti-scabies pill). These are not fancy new drugs. In fact, both have been in use for quite some years and are also prescribed for other parasitic infections. Ivermectin and permethrin both work by targeting the nervous system of the scabies mites. To function, nerve cells need to transmit electrical signals. These electrical signals can’t easily cross the cell membrane (the barrier separating the inside of the cell from the outside of the cell) and need specialized ‘portals’ to travel across. Ivermectin and permethrin block these portals specifically in the nerve cells of parasites, without impacting human nerve cells. This inactivates the nerve cells in the scabies mites, which results in paralysis and death of the mites. Though you might expect the itch to be worst when the scabies mites are actively digging through your skin, the itching sensation actually tends to intensify 1-2 weeks after treatment before resolving. This happens because cleaning the dead mites exposes the body to even more scabies mite molecules that induce an immune response, which temporarily worsens the itch.

Scabies now: forgotten again?

For Dutch students, it now feels like the peak itch days are in the past. In case of the itch of ’23, the outbreak was worsened because scabies was so rare in the Netherlands that it became a bit of a forgotten disease. But as scabies spread, word about it spread as well, and the taboo around it started to disappear. This caused a surge of useful information on how to recognize and treat scabies, making cases like my friend, who walked around with it for more than 5 months thinking it was eczema, more and more rare in my social circle. For me, in a few years, an itch will likely just be an itch again. However, as scabies has been around forever, it is everywhere, and it still causes a huge problem globally. Currently, over 200 million people worldwide are infected with scabies, and it is much more common in poorer regions of the world, especially amongst children. Though the available drugs can be very effective, they only work when the treatment regimen is followed meticulously, which demands resources that are not always widely accessible. Thus, research into better diagnosis, prevention, and treatment of scabies is still very much needed – so that an itch can go back to becoming just an itch. But then, for everyone!

Want to know more? Here are some interesting links:

• https://www.rivm.nl/en/scabies

  • Information page on the recognition and treatment of scabies.

• Roncalli RA. The history of scabies in veterinary and human medicine from biblical to modern times. Vet Herit. 1988 Feb;11(1):2-13. PMID: 11621488.

  • Old-school article that discusses the history of scabies.

• Arlian LG, Morgan MS. A review of Sarcoptes scabiei: past, present and future. Parasit Vectors. 2017 Jun 20;10(1):297. doi: 10.1186/s13071-017-2234-1. PMID: 28633664; PMCID: PMC5477759.

  • Review article that describes on the biology of the scabies mite.

• Jannic A, Bernigaud C, Brenaut E, Chosidow O. Scabies Itch. Dermatol Clin. 2018 Jul;36(3):301-308. doi: 10.1016/j.det.2018.02.009. Epub 2018 May 1. PMID: 29929601.

  • Insightful article that summarizes the different ways scabies causes itch.

• Bhat SA, Mounsey KE, Liu X, Walton SF. Host immune responses to the itch mite, Sarcoptes scabiei, in humans. Parasit Vectors. 2017 Aug 10;10(1):385. doi: 10.1186/s13071-017-2320-4. PMID: 28797273; PMCID: PMC5553898.

  • Overview article that describes the human immune responses to scabies.