Rash During Immunotherapy

Skin is one of the places immunotherapy most often shows up. Most rashes are manageable. But a small number are dangerous. The difference is not always obvious from the outside. That is why the National Cancer Institute (NCI) asks you to call rather than judge it yourself.

NCI describes the skin effect of immunotherapy in one line. It can cause "a severe and sometimes extensive rash. Your skin may be dry or blister."

On its page about immune-related organ inflammation, NCI adds a little. Skin problems "may include rashes, itchy skin, blisters, and sores."

So the range is wide. It runs from dryness and itching, through a red or darkened rash that may cover a wide area, to blistering and open sores. Itching with no visible rash also counts. It is worth mentioning.

Other treatments cause different patterns. Chemotherapy tends to cause dry, itchy, red or darker skin, a minor rash, easy sunburning, and nail changes. If you are on more than one treatment, say so. It changes what the rash likely is.

NCI groups skin problems among the more common immune-related effects of checkpoint inhibitor therapy. The digestive, endocrine, musculoskeletal and respiratory systems are on that list too. NCI does not attach a percentage. Honest reporting of frequency in plain-language sources is thin.

Drug labeling gives a narrower figure. In FDA labeling for pembrolizumab, "immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) adverse reactions." That figure covers reactions judged immune-mediated, and only for one drug. It does not cover every rash someone on immunotherapy might get, which is more common. Treat it as a floor, not a full picture.

Clinicians grade skin reactions by severity. Treatment decisions follow the grade. FDA labeling for pembrolizumab reports rash at Grade 2 and Grade 3 and ties action to it: "topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes." The drug is withheld or stopped for good "depending on severity." Systemic corticosteroids (steroids taken by mouth or by drip) were required in 40% (15/38) of patients with immune-mediated dermatologic reactions.

None of these sources publish a plain-language definition of each skin grade for patients. Grading a rash needs someone who can look at it and at your blood work. Describe what you see. Let your team assign the grade.

NCI's instruction for immunotherapy is specific: "If you have a severe, extensive, blistering, or painful rash and are receiving immunotherapy, call your doctor to get their advice. It's especially important to call about rashes that involve the eyes or a mucous membrane, such as your mouth."

Read that list carefully. Four features trigger a call: severe, extensive, blistering, or painful. Two locations raise it further: the eyes, and mucous membranes such as the mouth.

NCI also notes that how urgently you act differs by person: "Your oncologist may advise you to call him or her first about inflammatory symptoms, or you may be advised to seek emergency medical care." Settle which one applies to you before you need it.

MedlinePlus, from the National Library of Medicine, tells people taking pembrolizumab to "call your doctor immediately or get emergency medical treatment" for a list of serious effects. That list includes "blisters or peeling skin; skin redness; rash; itching," "painful sores or ulcers in mouth, nose, throat, or genital area," and "fever or flu-like symptoms; or swollen glands."

Skin plus fever is a pattern to take seriously. So is skin plus sores inside the mouth, nose, throat or genital area.

FDA labeling names the reactions behind that warning: "exfoliative dermatitis, including Stevens Johnson Syndrome, DRESS, and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies." The label tells clinicians to withhold the drug for suspected SJS, TEN or DRESS. It tells them to stop it for good once confirmed. These are rare. They are also the reason a peeling or blistering rash is never a wait-and-see problem.

Here is NCI's advice. Use mild soaps and only the skin products your team recommends. Moisturize with a recommended cream or lotion. Put it on while your skin is still damp after a short, lukewarm shower. Wear sunscreen and sun-protective clothing. Avoid products that contain alcohol or fragrance. Keep nails short and wear gloves for household tasks. Colloidal oatmeal baths can help with itching. Some chemotherapy also causes photosensitivity, meaning skin that burns easily in sunlight. So sun protection is not optional.

NCI advises writing down key information about your treatment. Keep it handy for the emergency room: the drug name or names, your doctor's contact information, and your hospital's contact information. An emergency clinician who does not know you are on a checkpoint inhibitor reads a rash very differently.

Autoimmune Side Effects (irAEs) From Immunotherapy, Side Effects Overview, and Steroid Side Effects During Cancer Treatment.

• National Cancer Institute — Skin and Nail Changes during Cancer Treatment: https://www.cancer.gov/about-cancer/treatment/side-effects/skin-nail-changes
• National Cancer Institute — Immunotherapy and Organ-Related Inflammation: https://www.cancer.gov/about-cancer/treatment/side-effects/organ-inflammation
• MedlinePlus (National Library of Medicine) — Pembrolizumab Injection: https://medlineplus.gov/druginfo/meds/a614048.html
• U.S. Food and Drug Administration — KEYTRUDA (pembrolizumab) prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125514s158lbl.pdf