CUTANEOUS SIDE EFFECTS

OF CHEMO AND
RADIOTHERAPY
BY DR MAJID KHAN
 OUTLINE
• Toxic erythema of chemotherapy
• Papulopustular eruptions
• Chemotherapy‐induced hair changes
• Chemotherapy‐induced nail changes
• Chemotherapy‐induced hyperpigmentation
• Chemotherapy‐induced hypopigmentation
• Photosensitivity
• Recall reaction
• Radiotherapy‐associated skin side effects
 •Commonly affected areas: palms, soles, major flexures.

TOXIC ERYTHEMA OF CHEMOTHERAPY

• Toxic Erythema of Chemotherapy (TEC) encompasses various cutaneous reactions to

chemotherapy agents.
• Occurs post-chemotherapy; simplifying terminology for overlapping reactions.
• Commonly affected areas: palms, soles, major flexures.
Pathophysiology
• Direct toxicity of chemotherapeutic agents excreted through eccrine ducts.
• High density of eccrine glands in palms/soles explains predilection.
• Other factors: temperature, friction, trauma, vascularity influence skin reactions.
• Clinical Features
• Presents 2 days to 3 weeks post-chemotherapy with pain, pruritus, erythematous patches, and
oedematous plaques.
• Distribution: acral skin, major flexures; may involve elbows, knees, ears.
• Late onset: seen in continuous low-dose infusions.
• Clinical Variants
• Palmoplantar Erythrodysaesthesia: tingling/burning sensation preceding eruption; resolves
post-treatment.
• Intertriginous Eruption: characterized by red papules, plaques; resolves with pigmentation
and desquamation.
• Neutrophilic Eccrine Hidradenitis: involves extremities, trunk, face, palms; resolves
spontaneously.
Differential Diagnosis
• Differentiate from drug hypersensitivity, graft-versus-host disease, infective intertrigo.
Prognosis & Management
• Recurrence possible with re-challenge or higher doses; can be reduced by dose
adjustments.
• Usually resolves spontaneously; no specific treatment required.
• Biopsy for diagnostic clarity; management is symptomatic; severe reactions may
require treatment cessation.
 PAPULOPASTULAR ERUPTIONS

• Papulopustular eruptions are drug-induced acneform dermatoses resembling acne vulgaris but
typically lacking a comedonal component.
• Also referred to as acneform eruptions.
• Incidence: Can occur in up to 90% of patients receiving EGFR inhibitors
Pathophysiology
• Caused by the inhibition of signal transduction pathways by targeted agents like EGFR
inhibitors.
• EGFR inhibition leads to premature differentiation of keratinocytes and subsequent
inflammatory responses.
Clinical Features
• Presentation within the first two weeks of treatment with symptoms like burning pain, pruritus.
• Lesion distribution: scalp, face, chest, back, extremities; lacks comedones.
Severity Classification
• CTCAE grading scale: Classifies severity based on the extent of body surface area affected and associated
symptoms.
• MASCC grading scale: Specific to EGFR inhibitor-induced toxicities.
Disease Course & Prognosis
• Severity can vary, with monoclonal antibodies causing more severe reactions.
• Typically resolves within two months post-treatment without scarring; potential for post-inflammatory
hyperpigmentation.
Differential Diagnosis

• Distinguish from drug-induced acne, folliculitis, and other related conditions.

Investigations
• Skin biopsy and swabs may aid in diagnosis, though not mandatory.
Management
• Discuss potential dermatological side effects with the patient before initiating treatment.
• Avoid excessive sun exposure; use high-protection sunscreen.
• Prophylactic skin treatments and active measures such as topical steroids, tetracycline
antibiotics, and isotretinoin for severe cases
 CHEMOTHERAPY INDUCED HAIR CHANGES

CHEMO INDUCED ALOPECIA

• Hair loss due to chemotherapy's impact on hair follicles.
• Common occurrence during cancer treatment.
• Chemotherapy's effect on rapidly dividing cells, including hair cells.
• Also emotional impact
• Sudden onset of hair loss as a key identification factor.

Coping Strategies
• Psychological support, counseling, and options like wigs or head coverings.
• cooling caps as a preventive measure. Note that there are no specific medications, but
minoxidil can help regrow hair.
CHEMO INDUCED HYPERTRICHOSIS
• Commonly associated with EGFR inhibitors.
• Manifests as facial hypertrichosis, changes in hair texture, and eye hair alterations.

Pathophysiology
• EGFR's role in regulating the hair growth cycle.
• Impacts the anagen phase of hair growth, resulting in changes during chemotherapy.

Clinical Features
• Hair texture, length, and thickness alterations during EGFR inhibitor treatment.
• Trichomegaly complication: Eyelash growth towards the eye, causing abrasions.
• Differential Diagnosis & Prognosis
• Differential diagnosis includes paraneoplastic hypertrichosis.
• Typically reversible hair changes within a month post-treatment cessation.
• Investigations & Management
• No specific investigations required for diagnosis.
• Management involves discontinuation of the responsible drug.
• Facial hirsutism management through temporary or permanent hair removal methods like
topical eflornithine or laser hair removal.
 CHEMO INDUCED NAIL CHANGES

• Common in long-term EGFR inhibitor treatment.

• Effects include Beau's lines, onychomadesis, leukonychia, and more.
• Pathophysiology
• Toxicity affects nail matrix epithelium, causing nail plate defects.
• Impacts nail bed epithelium and proximal nail fold integrity.
Clinical Presentation
• Nail biopsy rarely performed to assess changes.
• Various alterations: onycholysis, dystrophy, melanonychia, etc.
• EGFR inhibitor-related nail changes typically emerge in 1-2 months.
• Pain, tenderness, bleeding, and dry skin common symptoms.
• Severity Classification & Course
• Grading scale for adverse effects by EGFR inhibitors.
• Nail changes evident within 1-2 months, persist even after stopping treatment.
Prognosis & Investigations
• Nail changes may persist post-treatment cessation.
• Swabs for secondary infections; nail clippings for mycology.
Treatment & Recommendations
• Conservative management for most nail changes.
• Preventive Measures & Drug Withdrawal
• Comfortable footwear to reduce periungual trauma.
• Avoid drug withdrawal; managing nail changes takes time post-drug cessation.
 CHEMO INDUCED HYPERPIGMENTATION

• Increased skin pigmentation due to chemotherapy.

• Includes post-inflammatory hyperpigmentation, flagellate dermatosis.
• Incidence of flagellate hyperpigmentation with bleomycin: 8%-22%..
• Mechanisms: direct pigmentary effect, increased melanin production, etc.

Pathology & Clinical Features

• Histopathological changes in flagellate pigmentation.
• Flagellate hyperpigmentation with bleomycin.
• Fluorouracil, vinorelbine, and daunorubicin-induced pigmentation.
Differential Diagnosis
• Post-inflammatory hyperpigmentation, haemochromatosis, Addison's disease.
• Chemotherapy-induced hyperpigmentation often patchy and widespread.
Disease Course & Investigations
• Progression or limitation based on continued drug use.
• Reversibility after discontinuing the chemotherapy drug.
• Diagnosis via clinical history, identifying the culprit drug, and skin biopsy if needed.
Management
• No specific treatment for chemotherapy-induced hyperpigmentation.
• Expectation of slow disappearance post-drug cessation.
• Counselling patients about potential pigment changes.
Conclusion
• Hyperpigmentation prognosis tied to chemotherapy cessation.
• Itching management with antihistamines to limit trauma-induced hyperpigmentation.
 CHEMO INDUCED HYPOPIGMENTATION

• Includes post-inflammatory hypopigmentation, hypomelanosis.

• Various chemotherapeutic drugs linked to hypopigmentation.
• Unknown pathogenesis; hypotheses include genetic factors, lack of melanocyte growth factors.
Pathology & Clinical Features
• Histopathological absence of melanin and melanocytes.
• Hypopigmentation manifests as partial or total pigment loss.
• Symmetrical appearance resembling idiopathic vitiligo, often seen in distal digits.
Differential Diagnosis
• Includes idiopathic vitiligo and post-inflammatory hypopigmentation.

Disease Course & Investigations

• Onset of hypopigmentation from days to 6 months post-medication.
• Chemotherapy continuation despite progression of hypopigmentation.
• Persistence possible after drug discontinuation; Wood's light examination or skin biopsy for
diagnosis.
Management
• Sunblock advice to patients as a preventive measure.
 PHOTOSENSITIVITY

• Abnormal photosensitivity due to chemotherapy agents.

• Reactions categorized into phototoxic, photoallergic, and UV recall.
• Most common reaction is phototoxicity, followed by photoallergic and UV recall reactions.
Pathophysiology
• Chemotherapy-associated photosensitivity involves UV radiation absorption by photosensitizing
drugs.
• Phototoxic: Chemicals cause cell membrane and DNA damage.
• Photoallergic: UV radiation converts drugs into immunologically active compounds, triggering an
inflammatory response.
Pathology
• Phototoxic reaction: Spongiosis, necrotic keratinocytes, dermal edema, and mononuclear cell
infiltrate.
• Photoallergic reaction: Similar to allergic contact dermatitis, with spongiosis and lymphocytic
infiltrate.
Clinical Features
• Phototoxic reaction: Burning sensation, erythema, blistering, desquamation in light-exposed sites.
• Photo-onycholysis associated with mercaptopurine therapy.
• Photoallergic reaction: Eczematous reaction spreading beyond exposed areas.
Differential Diagnosis
• Other photosensitivity diseases considered in diagnosis.

Disease Course & Investigations

• Phototoxic reactions resolve within a week, while photoallergic reactions may last up to 3 weeks.
• Chemotherapy-induced photosensitivity resolves over weeks but hyperpigmentation may persist.

Management & Investigations

• Symptomatic treatment.
• Discontinuation or dose reduction of culprit chemotherapy agents for severe reactions.
• Topical steroids, broad-spectrum sunscreens, UV light-protective clothing recommended.
 RECALL REACTION
• Rare phenomenon: drug-induced inflammatory eruption in previously irradiated skin.
• Drug initiation days to years after ionizing radiation exposure.
• Anticancer agents, antibiotics, and simvastatin commonly implicated
Pathophysiology
• Unknown mechanism; proposed hypotheses include radiotherapy-induced mutations making skin
cells vulnerable to cytotoxic therapies.
• Potential idiosyncratic drug hypersensitivity reactions.
• Relationship between occurrence and applied radiation dose is absent.
• Pathology
• Specimens show ballooning degeneration of epidermal keratinocytes with inflammatory
infiltrate.
• Clinical Features
• Reaction affects previously quiescent, irradiated skin.
• Clearly corresponds to prior irradiated area; may spread but differentiated from incomplete
healing of ongoing reactions.
• Occurs more severely when drug exposure follows radiation closely.
• Differential Diagnosis
• Acute or chronic radiodermatitis, contact dermatitis, and photosensitivity should be considered.
• Disease Course & Prognosis
• Reactions settle within days of stopping the triggering drug; not always recurring upon re-challenge.
• Investigations
• Detailed history needed; skin biopsy may aid diagnosis.
• Management
• Severe reactions treated with systemic/topical steroids, anti-inflammatories, and antihistamines.
• Sun exposure minimization; discontinuation of triggering drug.
• Rechallenge may be possible with prophylactic oral corticosteroids or dose reduction.
 RADIATION INDUCED SKIN CHANGES

• Use of high-energy ionizing radiation (X-rays, electrons) to target cancer cells.

• Divided into external beam and internal radiotherapy.
• Commonly associated with skin side effects termed radiation dermatitis.
• Common occurrence: Majority of patients experience radiation dermatitis during breast cancer or head-neck
cancer radiotherapy.
• Risk factors: Obesity, poor nutrition, existing skin disease, prolonged/multiple radiation exposures, and certain
underlying syndromes.
Pathophysiology
• Skin damage due to radiation involves tissue injury, inflammatory cell recruitment, DNA damage, cytokine
release, and cellular apoptosis.
Clinical Features
• Manifests within days to weeks: Irradiated skin areas show sharply demarcated changes.
• Severity increases with cumulative radiation doses.
Acute Radiation Dermatitis
• Develops within 90 days: Erythema progressing to desquamation, necrosis, and mucositis in severe cases.
Chronic Radiation Dermatitis
• Occurs months to years later: Extends inflammatory changes, leading to skin atrophy, alopecia,
telangiectasia, and hypopigmentation.
Differential Diagnosis
• Psoriasis, bullous pemphigoid, infection, contact dermatitis, and radiation recall to be considered.
Severity Classification
• Grading (1-5) based on CTCAE criteria: ranges from mild erythema to severe ulceration and necrosis.

Investigations
• Clinical history and timing are often diagnostic; biopsy or skin swab if diagnosis is uncertain or infection is
suspected.
Management
• No evidence for preventive treatments; basic hygiene and emollients are initiated.
• Grades 1-3: Clean, dry, and topical applications including antiseptic creams, hydrophilic dressings, and moderate to
strong topical steroids.
• Integrated care approach involving oncologists, nurses, and dermatologists; regular assessment.
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