Introduction
Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients’ quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition.
Methods
We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study.
Results
The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP.
Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi
Case no
Demographics: age, race, and sex
Fitzpatrick skin type
Cancer type
EGFR therapy
Concomitant photosensitive drug(s)
Time to EDP (months)
Clinical features
Distribution
Symptoms
Treatments and clinical course
EDP status from most recent follow up
1
47 y/o Asian male
III
Stage IV NSCLC
Erlotinib
None
Unknown
Brown-blue-gray hyperpigmented patches
Bilateral shins
Left thigh
Xerosis
Pruritus
Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration
Tacrolimus 0.1% BID for 9 months, improvement but no resolution
Ongoing
2
62 y/o Asian female
IV
Stage IV NSCLC
Osimertinib
None
4
Gray-brown hyperpigmented patches
Bilateral arms
Back
Forehead
Neck
Right shin
None
Tacrolimus 0.1% ointment for 1 year with minor improvement
Ongoing
3
69 y/o Asian female
IV
Stage IV NSCLC
Osimertinib
None
4
Gray-brown macules and patches
Chest
Face
Forehead
Bilateral legs
None
Tacrolimus 0.1% ointment for 10 months, no improvement
Ongoing
4
79 y/o White male
II
Stage IV NSCLC
Osimertinib
None
15
Mottled grey-blue hyperpigmented patches and plaques with mild scaling
Bilateral arms
Back
Forehead
Neck
None
Photoprotection, no improvement
Ongoing
5
69 y/o Asian female
III
Stage IV NSCLC
Osimertinib
Ibuprofen
4
Blue-grey hyperpigmented macules and patches
Abdomen
Bilateral arms
None
Tacrolimus 0.1% ointment for 7 months, no improvement
Ongoing
6
65 y/o Asian male
III
Stage IV NSCLC
Osimertinib
None
20
Hyperpigmented blue gray macules and patches
Helix
Bilateral shins
None
Photoprotection, no improvement
Ongoing
7
66 y/o Asian female
IV
Stage IV NSCLC
Erlotinib
TMP-SMX
6
Ashy grey-brown thin plaques
Back
Forehead
None
2.5% hydrocortisone ointment for 8 months, resolved
Resolved
8
82 y/o Asian male
III
Stage III NSCLC
Erlotinib
Simvastatin
20
Ash-grey hyperpigmented patches
Dorsal feet
Forehead
Scalp
None
Photoprotection
Ongoing
9
57 y/o Asian female
III
Stage II NSCLC
Erlotinib
None
1
Bue-grey discoloration
Tongue
None
No intervention
Ongoing
10
51 y/o Asian female
III
Stage IV NSCLC
Osimertinib
None
9
Blue-grey hyperpigmented macules and patches
Bilateral arms
Axillae
Groin
Neck
Trunk
None
2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement
Ongoing
11
67 y/o Asian male
III
Stage IV NSCLC
Osimertinib
None
7
Gray-blue macules and patches with mild background erythema and scaling
Bilateral arms
Ears
Face
Bilateral shins
None
Triamcinolone 0.1% ointment, protection for 6 months with mild improvement
Ongoing
12
75 y/o Asian female
IV
Stage III NSCLC
Osimertinib
TMP-SMX
3
Gray-blue hyperpigmented patches
Bilateral arms
Abdomen
Back
Face
Bilateral shins
Pruritus
Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged
Triluma cream 6 months, mild improvement
Ongoing
13
42 y/o Asian male
IV
Stage IV NSCLC
Afatinib
TMP-SMX
24
Grey-brown hyperpigmented patches
Back
Face
None
Hydroquinone 4% cream for 2 years with mild improvement
Ongoing
14
74 y/o White female
III
Stage II NSCLC
Osimertinib
Atorvastatin
4
Grey-brown hyperpigmented patches
Bilateral legs
Trunk
None
Photoprotection
Ongoing
15
64 y/o Asian female
IV
Stage IV NSCLC
Osimertinib
None
3
Gray-brown hyperpigmentation
Abdomen
Bilateral arms
Back
Bilateral legs
Pruritus
Triamcinolone 0.1% cream; No change, minimal concern to patient
Ongoing
16
52 y/o Asian female
IV
Stage IV NSCLC
Osimertinib
None
42
Gray hyperpigmented patches with digitate shape
Abdomen
Bilateral flanks
None
Triamcinolone 0.1% cream
Ongoing
NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole
Conclusions
We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.
