Skin toxicity of chemotherapy drugs.

Why is it important to know about chemotherapy drugs and skin?

Every year 10.9 million people worldwide are diagnosed with Cancer, and that incidence is increasing. This increase reflects the growing world population and the fact that people live longer. Chemotherapy is a crucial component to all cancer management, and with this increasing burden of cancer, both clinicians and patients will see an increasing incidence of chemotherapy-related skin. toxicity.

What are the skin rashes associated with chemotherapy?

• Acral erythema
• Alopecia (hair lost)
• Photosensitivity (increased sensitivity to sunlight)
• Remember reactions
• Acneform (pimple type) rashes
• Skin necrosis
• Neutrophils eccrine hydradenitis
• Eccrine scaly metaplasia
• Hyperpigmentation
• Nail changes
• Mucositis
• Sclerotic dermal reactions
• Toxic erythema chemotherapy
• Vascular injury
• Xerosis
• Other reactions

Acral erythema

Acral erythema is also known as palmoplantar erythrodystesia (PPE) or hand-foot syndrome. It manifests as painful erythema (reddening of the skin) of the palms and soles, with or without bullas (large blisters). Swelling, tingling, hyperkeratosis, fissure and ulceration It can also happen. These symptoms may be preceded by dysesthesia (Altered skin sensation). The pain of this eruption It can be so severe that daily activities are limited.

If recognized early, the usual course of acral erythema is peeling (detachment of the outer layers of the skin) followed by re-epithelialization (new growth of the outer layers of the skin). The risk increases with each dose of chemotherapy.

The exact mechanism is unknown, but the skin of the hands and feet is postulated to favor a higher level of certain chemotherapy drugs that cause direct toxicity to skin cells.

Chemotherapy toxic erythema is a similar reaction that spreads to involve other sites, particularly intertriginous sites like armpits and groin, and knees.

What drugs are responsible?

The most associated medications include:

• Capecitabine
• Cyclophosphamide
• Cytarabine
• Daunorubicin
• Docetaxel
• Doxorubicin
• Etoposide
• Fluorouracil
• Floxuridine
• Hydroxyurea
• Idarubicin
• Interleukin-2
• Lapatinib
• Mercaptopurine
• Methotrexate
• Mitoxantrone
• Paclitaxel
• Sorafenib
• Sunitinib
• Tegafur
• Vinblastine
• Vincristine
• Vinorelbina

Acral Erythema Treatment

Often stopping or reducing the dose of the chemotherapy drug will result regression acral erythema for about 14 to 28 days. Supportive care may include wound dressings, analgesia (pain relief), and cold compresses.

Alopecia

Alopecia (hair loss) is the most common side effect of cancer treatment, and is often the most distressing to a patient's self-image. It occurs 7-10 days after treatment and continues to progress for 2-3 months.

There are two main ways that chemotherapy drugs cause alopecia:

• Anagen effluvium (most common): refers to the toxic effects on hair cells that divide rapidly
• Telogen effluvium: refers to increased shedding of normal hair cells

Alopecia is often temporary and resolves after stopping treatment, but some chemotherapy drugs like busulfan and cyclophosphamide can cause permanent hair loss.

What drugs are responsible?

Most chemotherapy drugs cause alopecia, but the most common culprits are:

• Taxanes (for example, paclitaxel and docetaxel)
• Anthracyclines (eg, doxorubicin, idarubicin, epirubicin, and mitoxantrone).

Treatment of drug-induced alopecia.

Various strategies have been tried to reduce alopecia, such as:

• Cooling the scalp to 24 ° C
• Using a headband to reduce the amount of chemotherapy given to the scalp
• Immune treatment to regulate upward cytokines (Hormone-like proteins secreted by cells)

Unfortunately, none have been consistently proven effective. It is important to inform patients about this possible side effect and provide a wig.

Other capillary abnormalities

Epidermal growth factor receiver Inhibitor treatment (EGFR) has been reported to slow down hair growth, brittle hair, and abnormally thick hair.

Photosensitivity

Certain chemotherapy drugs cause photosensitivity (increased sensitivity to sunlight) causing sunburn with minimal sun exposure.

What drugs are responsible?

The chemotherapy drugs that most commonly cause this are:

• Methotrexate
• Fluorouracil
• Dacarbazine

Treatment of drug-induced photosensitivity.

Patients should be informed of this possible side effect and protected from the sun. This involves the use of sunscreen and protective clothing.

Remember reactions

The term recall reaction refers to erythema (redness of the skin) in areas of previously inactive sunburn or radiotherapy. Sun exposure or radiation therapy may have been weeks or months ago and the skin may have fully recovered until the patient received chemotherapy.

The actual mechanism is not fully understood, but it has been postulated that it will occur as a result of recovery. keratinocytes (skin cells) damaged by chemotherapy drugs, since these cells divide and regenerate more quickly.

What drugs are responsible?

The most common medications that can cause this are:

• Gemcitabine
• Methotrexate
• Docetaxel
• Etoposide
• Doxorubicin

Treatment of recall reactions

Treatment involves minimizing sun exposure, good wound care. Possibly there is a role for current steroid creams to reduce inflammation.

Acne breakouts (such as pimples)

Also known as folliculitis, an acne reaction begins as facial erythema followed by papules (small bumps) and pustules (small pockets of pus) on the face and the upper part of the trunk. Unlike true acne, pustules are sterile (they do not contain bacteria)

What drugs are responsible?

Actinomycin D is the most common cause. Other drugs can also cause folliculitis, particularly epidermal growth factor receptor (EGFR) inhibitors such as gefitinib and cetuximab.

Management of acne reactions

Oral tetracycline antibiotics (eg, doxycycline) and topical antibiotics may help. Although bacteria don't seem to be involved in acne breakouts, these antibiotics do have an antiinflammatory effect above its antibacterial properties. Current retinoids And benzoyl peroxide can also help.

Skin necrosis

Skin necrosis is the term used to describe dead skin cells that turn black and peel off. Most chemotherapy drugs are toxic when exposed to the skin. Medications that must be delivered to the veins and arteries can leak into the subcutaneous tissue paper (extravasation)

There are two types of skin necrosis reaction:

• Irritants - The chemotherapy agent causes phlebitis (inflammation of the veins) and chemical cellulitis (inflammation of the deeper layers of the skin).
• Vesicants or blistering agents: The chemotherapy agent causes severe tissue necrosis (cell death), resulting in ulcers and eventual scar training.

What drugs are responsible?

Most chemotherapy drugs are irritating if extravasate. Doxorubicin is the most vesicant and can cause necrosis, ulceration and thrombosis (blood clots)

Skin necrosis treatment.

Local wound care and the use of cold compresses or thermal compresses can help with wound healing. When vesicants such as doxorubicin leak into the skin, early plastic surgical advice may be required due to the expected death of large areas of the skin.

Neutrophilic eccrine hydradenitis

Neutrophilic eccrine hydradenitis is characterized by sensitive red papules, plates or nodules on the trunk, face and ears. The diagnosis of this condition is based on the skin. biopsy and analyzing the histological (microscopic) changes. Neutrophils (a type of white blood cell) is seen around the eccrine glands (sweat).

High concentrations of chemotherapy drugs secreted in the sweat glands are believed to be the cause.

What drugs are responsible?

The most commonly implicated agents are:

• Cytarabine

• Bleomycin

Neutrophilic eccrine hydradenitis treatment

Neutrophilic eccrine hydradenitis often cures without treatment in days or weeks. Proper management involves performing a skin biopsy to help establish the diagnosis. Supportive treatment such as systemic Steroids, nonsteroidal pain relievers, and dapsone help to shorten the duration of the rash and relieve pain.

Eccrine squamous metaplasia

Eccrine squamous metaplasia is a rare skin reaction. It is also known as syringometaplasia and affects the upper part of the eccrine sweat duct. It presents as non-specific red plaques or as papularcrust eruption.

A distinctive subtype has been described that affects the armpits, groin, and sides of the neck.

What drugs are responsible?

Three large groups of chemotherapy drugs are known to cause this skin reaction.

• Nitrogen mustards p. cyclophosphamide, chlorambucil and melphalan
• Anthracyclines p. doxorubicin, idarubicin, and epirubicin.
• Antimetabolites, e.g. azathioprine, methotrexate, fluorouracil, and capecitabine

Treatment of eccrine squamous metaplasia

Treatment of eccrine squamous metaplasia is similar to that of neutrophilic eccrine hydradenitis. Spontaneous resolution generally occurs. It may reappear in approximately 50% when reintroducing chemotherapy with the same medications.

Hyperpigmentation (excessive darkening of the skin)

The most unique pattern of hyperpigmentation is flagellated hyperpigmentation caused by bleomycin. This reaction occurs as dark brown. linear stripes about 10 cm long and crisscrossed together in a pattern that resembles a flagellum (whip-like structure of certain bacteria that helps them move).

Various mechanisms have been reported to explain the cause of this hyperpigmentation. The most accepted hypothesis is that bleomycin induces pruritus (itching) of the trunk causing the patient to scratch. Scratching causes local accumulation of bleomycin in the skin.

What other drugs can cause hyperpigmentation?

Fluorouracil, vinorelbine, and daunorubicin can cause hyperpigmentation of the skin, nail and oral mucous membrane. Although it is not characteristically flagellated in nature, pigmentation caused by these agents can follow the distribution vein (called serpentine supravenous hyperpigmentation) or it may just be irregular and macular (non-specific flat color change).

Pigmentation treatment.

Oral antihistamines can be helpful if there is marked itching. Topical bleaching agents like hydroquinone can decrease melanin production and assistance in cleaning pigmentation areas. However, when the chemotherapy drug is discontinued, the pigmentation can be expected to slowly disappear without treatment.

Nail changes

There are several changes that can occur to the nail (nail diseases). This is due to the direct toxicity of the chemotherapy drug to the nail plate.

• Beau line - a transverse groove in the nail plate
• Onycholysis - separation of the nail plate from the underlying nail bed
• Onchomadesis: loss of the entire nail
• Nail pain, thickening and / or thinning.
• Hyperpigmentation or hypopigmentationleukonychia) - pale or dark streaks on the nail plate
• Paronychia

What drugs are responsible?

Two groups of chemotherapy drugs are particularly prone to causing nail changes:

• Taxanes p. docetaxel and paclitaxel
• Anthracyclines p. doxorubicin, idarubicin, and epirubicin.

You can also see changes in the nails with hydroxyurea.

Paronychia has also been observed and occurs with an incidence of 10-15% with EGFR therapy and <1% con la terapia con capecitabina. Aunque la terapia de apoyo es la mejor forma de tratamiento, ha habido cierto éxito con el uso de doxiciclina. En su forma más severa, un pyogenic granuloma it can happen.

Treatment of chemotherapy-induced nail changes

Often, changes in the nails disappear when the damaged nail is replaced by the growth of new nails. Optimal management may need to include pain relievers, as some of these nail changes can be extremely painful.

Mucositis

Mucositis refers to inflammation of mucous membrane Surfaces The lining of the mouth and gastrointestinal tract are extremely susceptible to damage by chemotherapy drugs due to the high rate of cell growth and regeneration. Up to 80% of chemotherapy patients experience this complication.

Symptoms begin with burning and erythema of the mouth followed by erosions and ulcerations that are intensely painful. Although the signs in the mouth are more obvious, any part of the gastrointestinal tract may be involved, so patients may also develop diarrhea.

What drugs are responsible?

Almost all chemotherapy drugs have the potential to cause mucositis, but the agents that affect DNA synthesis and are specific to the S phase (this is the synthesis phase of the cell cycle) causing the greatest amount of mucositis.

Examples include:

• Methotrexate
• Anthracyclines
• Cyclophosphamide

Mucositis treatment

Mucositis can rarely be life threatening and, when severe, may require the use of feeding tubes. The pain and discomfort of mucositis can have a major impact on the nutritional status of the patient.

Mucositis treatment is supportive and aimed at symptom control.

• Routine oral care:
  • Denture Removal
  • Gentle cleaning of the mouth and teeth.
  • Oral rises with salt and baking soda
  • Regular antiseptic and antifungal mouthwashes
• Mucosa lining agents:
  • Topical kaolin / pectin
  • Diphenhydramine
  • Oral antacids
  • Maltodextrin
• Analgesia
  • Pieces of ice
  • Topical local anesthetic solutions
  • Topical morphine sulfate in water
  • Oral analgesia or intravenous analgesia with opioids may be necessary in more extensive cases

Sclerotic skin reactions

Scar-like skin reactions that mimic morpho or systemic. sclerosis may accompany the use of bleomycin and docetaxel.

In some cases, these reactions have resolved after stopping the medication. The exact mechanism is unknown, but these drugs are postulated to increase the activity of fibroblasts on the skin

Vascular phenomenon Raynaud's phenomenon and vasculitis

Raynaud's phenomenon is an exaggerated response from the blood vessels at cold temperature or emotional stress. The symptoms are those of demarcated skin color changes of the digits.

Vasculitis refers to inflammation of the vessel walls and, as a result of this inflammation, there is a commitment to lumen of the vessel causing the tissue ischemia and necrosis.

Vasculitis can present as livedo reticularis, ulceration, and thromboembolism (blood clots)

What drugs are responsible?

Medications that cause Raynaud's phenomenon or vasculitis include:

• Bleomycin
• Cisplatin
• Gemcitabine

• Rituximab

Vasculitis treatment

The correct diagnosis of vasculitis is important and a skin biopsy aids in the diagnosis. Vasculitis treatment involves discontinuing the offending drug and the use of high-dose systemic corticosteroids.

Raynaud's phenomenon often improves with discontinuation of the drug. Simple measures like avoiding cold exposure, hand warmers, and wearing protective clothing are universally useful. Medications that can be used include calcium channel blockers and ACE inhibitors that promote vasodilation (opening) of the blood vessels in the fingers.

Xerosis

The xerosis (dry skin) is commonly seen in patients receiving epidermal growth factor receptor EGFR inhibitors). Sometimes dry skin can be seen with concomitant similar greasy scales seborrheic dermatitis. EGFR inhibitors are postulated to arrest the growth of keratinocytes (skin cells) and initiate terminal maturation. Mucous skin surfaces such as the vagina, mouth, and eyes can also be affected.

Other reactions

Like other drugs, chemotherapy drugs can cause other Adverse reactions, including:

• Anaphylaxis
• Drug hypersensitivity syndrome
• Fixed drug eruption
• Flagellate erythema
• Drug-induced photosensitivity
• Stevens Johnson syndrome and toxic epidermal necrolysis.
• Urticaria
• Edema (Swelling) - Edema of the face, eyelids, ankles and forearms has been reported with the use of multi-kinase inhibitors such as imatinib.
• Hypopigmentation - Pale skin patches have been reported with multi-kinase inhibitors and are more common in patients with darker skin types. In general, the pigmentary alteration is totally reversible in the reduction or withdrawal of the drug.