Striking rash in a patient with lung cancer on a checkpoint inhibitor

Discussion

Among multiple autoimmune complications, dermatologic toxicity is the most common immune-related adverse event, occuring in about 30% to 40% of patients^7,8 and with an average onset of 3-4 weeks after initiating treatment with checkpoint inhibitors.⁹ In addition to vitiligo, the most common type of rash described is a reticular maculopapular rash on the trunk and extremities.¹⁰ Other findings, such as photosensitivity, alopecia, xerosis, and hair color changes, have been reported in smaller numbers. Skin exfoliation, as seen in the present case, has been reported in fewer than 1% of the cases.⁴ Perivascular lymphocytic infiltrates extending deep into the dermis are most likely to be seen if the lesions are biopsied. Both the location of the rash in our patient and its relapsing nature are rare and make it more interesting as it presents a diagnostic dilemma for treating physicians. Ear, nose, and throat surgeons are more likely to encounter such a complication with the expanded use of PD-1 and PD-ligand 1 inhibitors in advanced head and neck cancers. The differential diagnosis includes localized eczema, psoriatic rash, skin infection, or an autoimmune phenomenon.

The location of the rash was also of concern because there have been reports of autoimmune inner-ear disease related to immunotherapy.¹¹ After the failure of treatment with empiric antibiotics and topical steroids, in addition to the development of a new rash on her abdomen, we concluded that this case might represent an unusual autoimmune skin complication. The resolution of the skin lesions in both locations (the ears and the abdomen) with the oral steroid therapy, supported our suspected diagnosis of autoimmune dermatitis.

It is essential that these complications are detected early and misdiagnosis is avoided because timely treatment with steroids will prevent progression to more severe problems such as Steven-Johnson syndrome, toxic epidermal necrolysis,¹² or extension into the inner ear.¹¹This case is part of a growing spectrum of other unusual cases seen with immunotherapy treatment, such as erythema nodosum-like reactions,¹³ bullous dermatitis,¹⁴ and psoriasiform eruptions.¹⁵ It highlights the need for an awareness of expanding dermatologic complications from immunotherapy beyond the reported common manifestations. Established guidelines and algorithms for the management of immune-related dermatologic toxicity are available to assist the physician in treatment (Table 1).¹⁶ Skin biopsy should be considered if the diagnosis remains uncertain, although starting empiric treatment with steroids is a widely acceptable approach. Reassessing the skin rash in 48 hours to 1 week after treatment initiation is crucial because steroid-refractory cases will need additional immunosuppression. Early termination of steroids is associated with higher recurrence rate, therefore tapering steroids over 4 weeks is highly recommended before resuming treatment with checkpoint inhibitors.

In summary, increased awareness among health care professionals of the common and unusual complications of immunotherapy agents is important and essential in patient care. In addition to oncologists, head and neck surgeons, pulmonologists, urologists, dermatologists, and general internists will encounter patients with immunotherapy-related complications. Patient education should be emphasized to ensure prompt investigation and treatment of complications. Finally, it is not yet clear whether the development of autoimmune reactions predicts disease response to treatment. In a series of 134 patients with lung cancer, the occurrence of autoimmune adverse events correlated with improved survival.¹⁷ More research is needed to identify prognostic and predictive biomarkers for response to immunotherapy.
 

Conclusion

This pattern of autoimmune dermatitis localizing to the ears is rare (<1% of cases of dermatitis). Nevertheless, it raises the awareness for dermatologic complications of immunotherapy beyond the classical reported manifestations. Prompt diagnosis and treatment is essential to avoid serious complications such as Steven-Johnson syndrome, toxic epidermal necrolysis, and potentially damage to the inner ear.