Alopecia Refractory Case Study
INTRODUCTION
Both scarring and nonscarring alopecias have been described with long-term use of epidermal growth factor receptor (EGFR) inhibitors. Current treatments revolve around anti-inflammatory agents such as topical corticosteroid ointments, creams, and intralesional injections to reduce follicular inflammation. Unfortunately, none of these therapies are universally effective. Here, we describe a case of erlotinib-induced alopecia refractory to intralesional and topical corticosteroids that was successfully treated with doxycycline as a novel treatment approach for EGFR inhibitoreassociated alopecia. CASE REPORT
A 77-year-old woman with a 4-year history of nonesmall cell lung cancer (NSCLC) was started on the EGFR inhibitor, erlotinib (initial dose of …show more content…
150 mg daily), for recurrence of her EGFR-mutated NSCLC after adjuvant chemotherapy.
She experienced the early papulopustular eruption on her face and chest within 2 weeks after initiating erlotinib therapy, which resolved after a month of minocycline and dose reduction of her erlotinib to 100 mg daily, but otherwise she tolerated erlotinib without further dermatologic concerns. However, 5 months after initiating erlotinib, localized asymptomatic alopecia developed over her right parietal scalp. Physical examination found a 5- x 3-cm area of alopecia with peripheral crusting and scale that was clinically consistent with an erosive pustular form of EGFR inhibitoreassociated alopecia.
After her diagnosis, the patient received multiple therapies including bimonthly intralesional triamcinolone injections, daily topical triamcinolone acetonide cream 0.1%, and daily topical clobetasol solution for 1 year, all of which were unsuccessful.
Her alopecia worsened despite treatment and spread to her left parietal scalp. At the peak of involvement, she exhibited an 8- x 8-cm area of hair loss with erythema, yellow crusting, and scale over her bilateral parietal scalp areas (Fig 1). ½F1
Because of her continued scalp
inflammation, lack of improvement on skin-directed corticosteroids, and a culture swab that grew Staphylococcus aureus, the patient was started on 100 mg of oral doxycycline twice daily with discontinuation of her other skin therapies. She reported dramatic improvement of her alopecia with regression of the lesions, evidence of hair partial regrowth, and resolution of crusting within 1 to 2 weeks of starting the medication, and her doxycycline was decreased to 50 mg twice a day 6 weeks after initiating treatment. Physical examination found diminishing areas of noninflamed scarring alopecia with hair partial regrowth on the right parietal and left parietal scalp and no associated serous drainage or crust
(Fig 2). ½F2
At her 6-month follow-up visit after initiating doxycycline, there were no signs of relapse of her alopecia and no evidence of recurrence of the scalp crust and drainage. Given the favorable results of her doxycycline and erlotinib regimen, her doxycycline was discontinued after a total 6-month treatment course, and, to date, the improvement has been maintained. She was able to continue her erlotinib at100 mg throughout without a change in dosage and was satisfied with the outcome of her treatment.
DISCUSSION
EGFR overexpression is a common feature of several different types of cancers, including lung, pancreas, breast, and colon, and correlates with both cancer progression and worsening prognosis.1 EGFR
Q3 inhibitors are antibodies or small molecules developed to target EGFR overexpression and slow the progression of malignancy. Because the EGFR signaling cascade is also highly involved in the homeostasis of epidermal keratinocytes and hair follicles in the skin,2 a variety of cutaneous side effects from EGFR inhibitor administration has been reported. The most common of these side effects include acneiformeruption (85% of patients), xerosis
(35%), paronychia (10%e15%), and mucositis
(rare).3 These cutaneous manifestations are a source of significant physical and emotional discomfort for patients. EGFR signaling is involved in the initiation of the anagen phase of the hair cycle, thus, acting as an important regulator of the hair growth phase.
Disruption of this phase with EGFR inhibitors leads to disorganized formation of the hair follicle and manifests as abnormalities such as finer, curlier, and more brittle hair and both scarring and nonscarring alopecia.3 Alopecia is a late manifestation of EGFR inhibitoreassociated dermatologic side effects, typically arising 2 to 3 months after initiation of the medication, and is characterized by significant inflammation of the scalp with recruitment of lymphocytes, plasma cells, neutrophils, and eosinophils on histologic examination.4 This inflammation is thought to arise from inhibition of EGFR from its normal role of suppressing free radical synthesis, thus, resulting in activation of the inflammatory cascade and leading to follicle destruction and alopecia.5
Current treatments for EGFR inhibitoreassociated alopecia center on inflammation modulation with local anti-inflammatory agents, such as topical hydrocortisone, steroid shampoos, and steroid lotions,6 none of which are universally effective. In a review of 11 cases of EGFR inhibitoreassociated alopecia,
Toda et al4 concluded steroids alone were not an effective treatment and that reduction or discontinuation of the EGFR inhibitor was needed in most cases to prevent scarring. The clinical practice guidelines for the prevention and treatment of
EGFR inhibitoreassociated dermatologic toxicities similarly do not describe any established interventions to reduce or prevent alopecia.5 Current recommended therapies are largely supportive and consist mainly of approaches to reduce inflammation and reduction or discontinuation of EGFR inhibitor therapy as a last resort. Unfortunately, for our patient, discontinuation of erlotinib was not a favorable option given its efficacy against her recurrent
NSCLC.
Doxycycline, as a member of the tetracycline family, inhibits key proinflammatory mediators such as nitric oxide and the mitogen-activated protein kinase pathway.7 These anti-inflammatory effects of doxycycline may contribute to its success in treating
EGFR inhibitoreassociated alopecia. In addition, doxycycline is a potent broad-spectrum antibiotic with good coverage of skin flora. Patients undergoing
EGFR-inhibitor treatment frequently have superinfections at sites of toxicity. In one study, 84 of 221(38%) patients had culture-positive Staphylococcus aureus superinfections after treatment with EGFR inhibitors.8 S aureus infection has also been linked to exacerbations of EGFR inhibitoreinduced skin eruptions, including that of a papulopustular eruption on the scalp with associated alopecia.9 Minocycline, another tetracycline, was reported to help in one case of folliculitis decalvansetype alopecia associated with erlotinib10; however, within the tetracycline family, doxycycline has been linked to fewer severe toxicities and is safer in patients with renal impairment than minocycline.
The success of doxycycline in treating our patient’s
EGFR inhibitoreassociated alopecia may be a combination of its potent anti-inflammatory and antibiotic properties. Although further studies are required, doxycycline should be considered a potential therapeutic option for corticosteroid-resistant
EGFR inhibitoreinduced alopecia.
Both scarring and nonscarring alopecias have been described with long-term use of epidermal growth factor receptor (EGFR) inhibitors. Current treatments revolve around anti-inflammatory agents such as topical corticosteroid ointments, creams, and intralesional injections to reduce follicular inflammation. Unfortunately, none of these therapies are universally effective. Here, we describe a case of erlotinib-induced alopecia refractory to intralesional and topical corticosteroids that was successfully treated with doxycycline as a novel treatment approach for EGFR inhibitoreassociated alopecia. CASE REPORT
A 77-year-old woman with a 4-year history of nonesmall cell lung cancer (NSCLC) was started on the EGFR inhibitor, erlotinib (initial dose of …show more content…
150 mg daily), for recurrence of her EGFR-mutated NSCLC after adjuvant chemotherapy.
She experienced the early papulopustular eruption on her face and chest within 2 weeks after initiating erlotinib therapy, which resolved after a month of minocycline and dose reduction of her erlotinib to 100 mg daily, but otherwise she tolerated erlotinib without further dermatologic concerns. However, 5 months after initiating erlotinib, localized asymptomatic alopecia developed over her right parietal scalp. Physical examination found a 5- x 3-cm area of alopecia with peripheral crusting and scale that was clinically consistent with an erosive pustular form of EGFR inhibitoreassociated alopecia.
After her diagnosis, the patient received multiple therapies including bimonthly intralesional triamcinolone injections, daily topical triamcinolone acetonide cream 0.1%, and daily topical clobetasol solution for 1 year, all of which were unsuccessful.
Her alopecia worsened despite treatment and spread to her left parietal scalp. At the peak of involvement, she exhibited an 8- x 8-cm area of hair loss with erythema, yellow crusting, and scale over her bilateral parietal scalp areas (Fig 1). ½F1
Because of her continued scalp
inflammation, lack of improvement on skin-directed corticosteroids, and a culture swab that grew Staphylococcus aureus, the patient was started on 100 mg of oral doxycycline twice daily with discontinuation of her other skin therapies. She reported dramatic improvement of her alopecia with regression of the lesions, evidence of hair partial regrowth, and resolution of crusting within 1 to 2 weeks of starting the medication, and her doxycycline was decreased to 50 mg twice a day 6 weeks after initiating treatment. Physical examination found diminishing areas of noninflamed scarring alopecia with hair partial regrowth on the right parietal and left parietal scalp and no associated serous drainage or crust
(Fig 2). ½F2
At her 6-month follow-up visit after initiating doxycycline, there were no signs of relapse of her alopecia and no evidence of recurrence of the scalp crust and drainage. Given the favorable results of her doxycycline and erlotinib regimen, her doxycycline was discontinued after a total 6-month treatment course, and, to date, the improvement has been maintained. She was able to continue her erlotinib at100 mg throughout without a change in dosage and was satisfied with the outcome of her treatment.
DISCUSSION
EGFR overexpression is a common feature of several different types of cancers, including lung, pancreas, breast, and colon, and correlates with both cancer progression and worsening prognosis.1 EGFR
Q3 inhibitors are antibodies or small molecules developed to target EGFR overexpression and slow the progression of malignancy. Because the EGFR signaling cascade is also highly involved in the homeostasis of epidermal keratinocytes and hair follicles in the skin,2 a variety of cutaneous side effects from EGFR inhibitor administration has been reported. The most common of these side effects include acneiformeruption (85% of patients), xerosis
(35%), paronychia (10%e15%), and mucositis
(rare).3 These cutaneous manifestations are a source of significant physical and emotional discomfort for patients. EGFR signaling is involved in the initiation of the anagen phase of the hair cycle, thus, acting as an important regulator of the hair growth phase.
Disruption of this phase with EGFR inhibitors leads to disorganized formation of the hair follicle and manifests as abnormalities such as finer, curlier, and more brittle hair and both scarring and nonscarring alopecia.3 Alopecia is a late manifestation of EGFR inhibitoreassociated dermatologic side effects, typically arising 2 to 3 months after initiation of the medication, and is characterized by significant inflammation of the scalp with recruitment of lymphocytes, plasma cells, neutrophils, and eosinophils on histologic examination.4 This inflammation is thought to arise from inhibition of EGFR from its normal role of suppressing free radical synthesis, thus, resulting in activation of the inflammatory cascade and leading to follicle destruction and alopecia.5
Current treatments for EGFR inhibitoreassociated alopecia center on inflammation modulation with local anti-inflammatory agents, such as topical hydrocortisone, steroid shampoos, and steroid lotions,6 none of which are universally effective. In a review of 11 cases of EGFR inhibitoreassociated alopecia,
Toda et al4 concluded steroids alone were not an effective treatment and that reduction or discontinuation of the EGFR inhibitor was needed in most cases to prevent scarring. The clinical practice guidelines for the prevention and treatment of
EGFR inhibitoreassociated dermatologic toxicities similarly do not describe any established interventions to reduce or prevent alopecia.5 Current recommended therapies are largely supportive and consist mainly of approaches to reduce inflammation and reduction or discontinuation of EGFR inhibitor therapy as a last resort. Unfortunately, for our patient, discontinuation of erlotinib was not a favorable option given its efficacy against her recurrent
NSCLC.
Doxycycline, as a member of the tetracycline family, inhibits key proinflammatory mediators such as nitric oxide and the mitogen-activated protein kinase pathway.7 These anti-inflammatory effects of doxycycline may contribute to its success in treating
EGFR inhibitoreassociated alopecia. In addition, doxycycline is a potent broad-spectrum antibiotic with good coverage of skin flora. Patients undergoing
EGFR-inhibitor treatment frequently have superinfections at sites of toxicity. In one study, 84 of 221(38%) patients had culture-positive Staphylococcus aureus superinfections after treatment with EGFR inhibitors.8 S aureus infection has also been linked to exacerbations of EGFR inhibitoreinduced skin eruptions, including that of a papulopustular eruption on the scalp with associated alopecia.9 Minocycline, another tetracycline, was reported to help in one case of folliculitis decalvansetype alopecia associated with erlotinib10; however, within the tetracycline family, doxycycline has been linked to fewer severe toxicities and is safer in patients with renal impairment than minocycline.
The success of doxycycline in treating our patient’s
EGFR inhibitoreassociated alopecia may be a combination of its potent anti-inflammatory and antibiotic properties. Although further studies are required, doxycycline should be considered a potential therapeutic option for corticosteroid-resistant
EGFR inhibitoreinduced alopecia.