Cutaneous side effects of EGFR and protein kinase inhibitors

What are EGFR inhibitors?

Epidermal growth factor receiver (EGFR) inhibitors are a new group of drugs developed to treat a wide range of cancers. EGFR overexpression in approximately 30% of cancers is one reason for their cell excess proliferation and tumor increase.

Although effective in treating many types of cancer, EGFR inhibitors often result in Adverse reactions on the skin, which occurs in at least half of treated patients.

Side effects are helping scientists learn more about skin disorders. In some cases, the presence of an adverse skin reaction indicates that the drug is effective in treating the tumor.

People can be treated with these drugs for long periods and will have to weigh the benefits against the side effects.

What are protein kinase inhibitors?

Protein kinases are enzymes inside the cell resulting in cellular proliferation. Protein kinase inhibitors reduce cell proliferation. point to amino acids tyrosine, threonine and serine. Some EGFR inhibitors are also protein kinase inhibitors.

How do these inhibitors work?

EGFR inhibitors are specifically directed against EGFR on the outside of the cell. Protein kinase inhibitors target protein kinases inside the cell. The specific receptors found in the Cancer determine which medication is likely to be beneficial.

• EGFR is found in the cell membrane. By binding with an epidermal growth factor ligand outside the cell, they activate a protein kinase inside the cell.
• Protein kinase prevents the phosphorylation of the specific protein. amino acidslike tyrosine.

EGFR and kinase inhibitors may be particularly useful in cancer therapy as they are less toxic than more traditional chemotherapies. Specific drugs target different types of cells and can be monoclonal antibodies with the suffix -mab or small molecules with the suffix -nib.

EGFR = epidermal growth factor receptor; PDGFR = plateletderived growth factor receptor; VEGFR = vascular endothelial growth factor receptor

There is currently great interest in the small molecule mutated B-RAF inhibitors, vemurafenib and dabrafenib, which are effective in the treatment of B-RAF-positive metastases. melanoma. B-RAF is a specific protein threonine kinase.

Many more EGFR and protein kinase inhibitors are in development.

Which are the cutaneous side effects of EGFR monoclonal antibody inhibitors?

The most common skin side effects of EGFR monoclonal antibody inhibitors are:

Folliculitis

Folliculitis (inflamed hair follicles) occurs in up to 40-85% of patients. It is an early event, usually seen within the first ten days of treatment. Sterile inflammatory papules and pustules seen predominantly in the T-zone of the face, but can be more extended involving the chest and back. Occasionally the scalp and pubic regions are involved or rarely the entire body.

Folliculitis is especially common and often severe with cetuximab. The intensity of folliculitis can fluctuate even when you continue to take the drug.

Folliculitis is often managed with:

• camouflage cosmetics
• Current antibiotics
• Oral antibiotics

• Topical steroids

If the folliculitis is severe, the medication may need to be stopped and it will resolve. The iIncidence and severity of inhibitor-induced EGFR follicular Reactions are halved by pretreatment with doxycycline or minocycline. These tetracycline medications may also be prescribed once you eruption has occurred allowing continued treatment with the EGFR inhibitor drug.

Alopecia and trichomegaly

Drug-induced alopecia (hair loss) is less common than folliculitis and tends to occur later, usually by 2-3 months. Patients may find that their hair becomes fine and brittle. They may experience frontal-temporary hair loss similar to male pattern baldness. This may or may not improve if the drug is stopped.

In contrast, patients often experience excessive growth of facial hair and eyelashes (hypertrichosis, trichomegaly).

Dry Skin (xerosispulpitis)

dry skin is predominant and handled with emollients. These drugs can cause pulpitis with pain fissures at the fingertips.

Dry skin sometimes seems seborrheic dermatitis.

Paronychia

Paronychia refers to painful inflammation of the nail folds. The fingers are affected more often than the toes. Paronychia can sometimes resolve on its own even with continued use of the drug, but it quickly disappears on discontinuation.

Treatment involves avoiding trauma such as tight shoes, avoiding excessive trimming or nail biting, and wearing appropriate footwear. Topical steroids and antiseptics can help. It is essential to treat the secondary. bacterial and mushrooms infection.

Skin cancer

Squamous cell carcinomas and multiple keratoacanthomas have been reported to arise in patients treated with sorafenib and other EGFR inhibitors.

What are the side effects of small molecule tyrosine kinase inhibitors?

Small molecule kinase inhibitors often block multiple enzymes, which means there is crossover in the actions and side effects of these drugs.

The most common side effects are:

• nonspecific rashes
• Newspaper edema
• Acral erythema
• Splinter hemorrhage
• Pigmentation changes
• Photosensitivity

the same side effects can also arise with monoclonal antibodies.

nonspecific rashes

Imatinib induces a rash in one third of patients who start taking it, but this rash is usually self-limiting. Imatinib has rarely been associated with vasculitisSteven Johnson syndrome/ Ten and acute generalized exanthematous pustulosis (AGEP)

A red facial rash is commonly seen in the first two weeks of treatment with sorafenib. It can look a lot like seborrheic dermatitis and usually resolves without treatment. It may be associated with tingling of the scalp or dysesthesia.

facial swelling

Swelling (edema) of the eyelids and face is common with imatinib and sunitinib. Edema can also affect the lower legs, lungs (pleural spills) and brain (cerebral edema).

Acral erythema

Acral erythema (red hands and feet) is commonly seen with sorafenib and sunitinib. Presents as painful symmetrical Palms and soles red and swollen. These drugs can also cause keratoderma/ /hyperkeratosis (excessive scale) and peeling (peeling). Acral erythema tends to appear two to four weeks after starting treatment and is dose-dependent. It improves rapidly on stopping the drug and may not recur on restarting it.

Small molecule kinase inhibitors tend to cause less extensive but more scaly acral erythema than that induced by the standard chemotherapy (hand and foot syndrome or palm–plant erythrodysesthesia).

Preventive measures include proper footwear to avoid injury to pressure areas. Discomfort may require a brief interruption of treatment.

Splinter hemorrhages

Without pain distal splinter hemorrhages are common, particularly affecting the fingernails. It has been suggested that they are due to inhibition vascular endothelial growth factor receptor (VEGFR). VEGFR is believed to be involved in the repair of the delicate coil. capillaries under the nail, which are subject to frequent injury.

Changes in hair and skin pigmentation.

Depigmented or white hair is usually noticeable after one month of sunitinib treatment. It is reversible with restoration of hair color two to three weeks after treatment is stopped.

Kinase inhibitors can lead to local or diffuse hypopigmentation (white skin or leucoderma) and hyperpigmentation (dark spots)

Photosensitivity

Protein kinase inhibitors can cause sunburn after minimal sun exposure (drug-induced photosensitivity).