Subacute Cutaneous Lupus Erythematosus-Like Eruption Induced by Durvalumab: A Case Report and Literature Review

Figures & data

Figure 1 Multiple dusky red to brownish papules and patches covered by scales and crusts with some erosions predominately on face (A), upper chest (B), back (C), and dorsum of both forearms (D).

Figure 2 Superficial perivascular infiltration of lymphocytes and melanophages with marked interface change, H&E 100X (A) Epidermal atrophy and few atypical basal keratinocytes, H&E 400X (B).

Abbreviation: H&E, hematoxylin and eosin.

Figure 3 One month after Durvalumab was discontinued, the lesions resolved with post inflammatory hyperpigmentation on face (A), upper chest (B), back (C), and dorsum of both forearms (D).

Table 1 Review of Reports on Checkpoint Inhibitors-Associated CLE

Study	Age (yrs)/Sex	Tumor Type	History of Autoimmune Disease	ICIs	Time to Rash Onset	Cutaneous Manifestations	Autoimmune Serologies	Histologic/DIF Results	Treatment	ICI Interruption	Follow-Up
Our case	74/M	SCLC	None	Durvalumab	3 infusion cycles (2 mo)	Multiple dusky red to brownish papules and patches with scale and erosions on the face, neck, trunk, and extensor surface of upper extremities	ANA: 1:320, fine speckled pattern Anti-Ro (SSA): positive Anti-La (SSB): negative Anti-dsDNA: negative Anti-Smith: negative	H&E: superficial perivascular infiltration, epidermal atrophy with marked interface change Thin epidermis was necrosed and separated with dysmaturation of atypical basal keratinocytes DIF: NA	HCQ 200 mg/day, prednisolone 1 MKD, low-potency topical corticosteroid	Permanently discontinued	Improved within 1 mo
Liu et al 2018^Citation25	58/F	NSCLC	AIHA	Nivolumab	5 mo	Monomorphous, violaceous papules and polycyclic, annular papulosquamous plaques on the back and chest	ANA: NA Anti-Ro (SSA): positive Anti-La (SSB): NA Anti-dsDNA: NA Anti-cardiolipin: positive	H&E: epidermal atrophy, interface dermatitis with lymphocytic and histiocytic infiltrate, moderate basal vacuolar damage, and colloid bodies DIF: negative	HCQ 400 mg/day, prednisolone 37.5 mg/day, superpotent topical corticosteroid	Discontinued and restarted 5 months later	Improved
Blakeway et al 2019^Citation20	Case 1 79/F	Melanoma	None	Pembrolizumab	3 infusion cycles	Annular scaly rash on the face, arms, torso, and legs	ANA: negative Anti-Ro (SSA): NA Anti-La (SSB): NA Anti-dsDNA: NA	H&E: vacuolar interface pattern, colloid bodies in the spinous and basal layers, and moderately dense perivascular infiltrate of lymphocytes in upper dermis DIF: granular deposition of C3 in the BMZ	Superpotent topical corticosteroid	Discontinued and restarted with no recurrence	Improved within 3 weeks
	Case 2 75/M	Melanoma	None	Pembrolizumab	9 infusion cycles	Widespread, symmetrical “lupus-like” dermatosis on the torso, arms and legs	ANA: negative Anti-Ro (SSA): NA Anti-La (SSB): NA Anti-dsDNA: NA	H&E: vacuolar interface pattern, colloid bodies in the spinous and basal layers, mildly dense perivascular infiltrate of lymphocytes in upper dermis, and increased dermal mucin DIF: granular deposition of IgG, IgA and IgM in the BMZ	Superpotent topical corticosteroid	Discontinued and restarted with no recurrence	Improved within 3 weeks
Zitouni et al 2019^Citation24	Case 1 72/F	Melanoma	Autoimmune hepatitis	Nivolumab	13 infusion cycles plus 2 mo after ICI discontinuation	Pruritic, nummular erythematous plaques on the back and arms	ANA: 1:640 Anti-Ro (SSA): positive Anti-La (SSB): positive Anti-dsDNA: negative	H&E: lymphoid inflammatory infiltrates predominantly in perivascular areas, and focal lesions of the dermis and epidermis DIF: no C3 or IgG depositions	HCQ 400 mg/day	Permanently discontinued	Improved within 4 mo
	Case 2 43/M	NSCLC	None	Nivolumab	2 infusion cycles (1 mo)	Annular erythematous eruption on the dorsal aspect of the hands, arms, and chest	ANA: 1:320 Anti-Ro (SSA): >600 IU/mL Anti-La (SSB): NA Anti-dsDNA: NA	H&E: discrete lymphoid perivascular inflammatory infiltrates DIF: scarce C3 deposits along the BMZ	HCQ 400 mg/day, prednisolone 1 MKD, potent topical corticosteroid	Permanently discontinued	Severe flare-up after 2 weeks of the treatment
Kosche et al 2019^Citation26	75/F	Serous ovarian cancer	None	Ipilimumab and Nivolumab	2 infusion cycles	Pruritic, erythematous, red-brown, scaly plaques with an arcuate appearance on the back, abdomen, arms, and legs	ANA: 1:160, speckled pattern Anti-Ro (SSA): >8.0 Anti-La (SSB): negative Anti-dsDNA: negative Anti-Smith: negative	H&E: interface lymphocytic infiltrate and focal basal vacuolar change DIF: NA	HCQ 400 mg/day, quinacrine 100 mg/day, prednisone 40 mg/day, mid-strength topical corticosteroid	Discontinued and switched to pembrolizumab	Improved within 1 week and later flared up
Ogawa-Momohara et al 2020^Citation22	80/M	Melanoma	None	Pembrolizumab	5 infusion cycles	Multiple annular erythema on the trunk	ANA: NA Anti-Ro (SSA): positive Anti-La (SSB): NA Anti-dsDNA: negative	H&E: strong liquefaction degeneration and dense superficial dermal and perivascular lymphocytic infiltration DIF: no C3 or IgG depositions	Prednisolone 1 MKD, topical corticosteroid	Discontinued at the 9th cycle	Improved within 3 mo
Marano et al 2019^Citation27	Case 1 60/M	SCLC	None	Nivolumab	2 infusion cycles (2 weeks)	Pruritic, erythematous macules and scaly papules coalescing into annular plaques on photo-distributed areas	ANA: 1:40 Anti-Ro (SSA): positive Anti-La (SSB): NA Anti-dsDNA: NA	H&E: interface dermatitis Colloidal iron staining: increased dermal mucin DIF: NA	HCQ 400 mg/day, prednisone 60 mg/day, potent topical corticosteroid	Discontinued and restarted	Improved
	Case 2 60/F	NSCLC	None	Pembrolizumab	3 infusion cycles (6 weeks)	Painful and pruritic, edematous, crusted and scaly erythematous papules coalescing into plaques on the face, upper back, chest, arms, forearms, and interphalangeal areas on the dorsal hands	ANA: 1:2560 Anti-Ro (SSA): positive, Anti-La (SSB): positive Anti-dsDNA: NA Anti-histone: positive	H&E: interface dermatitis with adnexal involvement and increased dermal mucin DIF: IgG, IgA, IgM cytoid bodies, linear fibrin deposits at the BMZ, and granular IgG and C3 staining	Prednisone 60 mg/day, intravenous infliximab, topical corticosteroid	Permanently discontinued	Improved within 1 mo
Bui et al 2021^Citation9	Case 1 54/F	SCLC	ICI-associated psoriasis	Nivolumab	20 mo	Annular eruption on the trunk and extremities	ANA: 1:5120, speckled pattern Anti-Ro (SSA): >8.0 Anti-La (SSB): >8.0 anti-dsDNA: negative	H&E: focal interface dermatitis, focal lichenoid dermal lymphocytes infiltrate, and mild dermal mucin deposition DIF: NA	HCQ 200 mg/day, potent topical corticosteroid	Continued with no interruption	Complete clearance within 6 mo
	Case 2 54/F	Ovarian cancer	None	PD-1 inhibitor	4 mo	Annular eruption on the upper extremities and trunk	ANA: negative Anti-Ro (SSA): negative Anti-La (SSB): negative Anti-dsDNA: negative	H&E: interface dermatitis, epidermal spongiosis, superficial dermal perivascular lymphocytes infiltrate with rare eosinophils, follicular plugging and subtle dermal mucin deposition DIF: granular C3, IgM, and IgG along the BMZ	Potent topical corticosteroid	Discontinued and restarted 1 month later	Improved within 2 mo
	Case 3 57/F	Breast cancer	ICI-associated Sjogren’s syndrome	Atezolizumab	11.5 mo	Annular eruption on the upper extremities and trunk	ANA: 1:320, speckled pattern Anti-Ro (SSA): >8.0 Anti-La (SSB): negative Anti-dsDNA: negative	H&E: interface dermatitis, focal lichenoid infiltrate, superficial to mid-dermal perivascular lymphocytic infiltrate, perifollicular plugging and increased dermal mucin deposition DIF: negative	Superpotent topical corticosteroid	Permanently discontinued 2 mo prior to rash onset for colitis	Improved within 1 mo
	Case 4 65/M	SCLC	None	Pembrolizumab	3 mo	Eruption on the trunk and extremities	ANA: 1:320, speckled pattern Anti-Ro (SSA): >8.0 Anti-La (SSB): negative Anti-dsDNA: NA	H&E: prominent interface dermatitis, focal vesicle formation, lichenoid infiltrate, prominent dyskeratotic keratinocytes with epidermal necrosis, and superficial to mid-dermal perivascular, periadnexal lymphocytic infiltrate and follicular plugging DIF: negative	HCQ 400 mg/day, potent topical corticosteroid	Permanently discontinued	Improved within 2 mo
	Case 5 60/M	Melanoma	None	Nivolumab	0.5 mo	Annular eruption on the extremities and trunk	ANA: 1:320, speckled pattern Anti-Ro (SSA): >8.0 Anti-La (SSB): negative Anti-dsDNA: NA	H&E: prominent interface dermatitis, lichenoid infiltrate, clefting, prominent superficial to deep dermal perivascular, periadnexal lymphocytic infiltrate and increased dermal mucin deposition DIF: negative	Potent topical corticosteroid	Continued with no interruption	Improved within 2 mo
Takeda et al 2021^Citation28	49/F	Oropharyngeal carcinoma	None	Pembrolizumab	2 weeks	Persistent erythema, and purple discoloration on the fingers, lower legs, and feet	ANA: 1:1280, speckled pattern Anti-Ro (SSA): positive Anti-La (SSB): NA Anti-dsDNA: negative Anti-Smith: positive Anti-phospholipid: negative ANCA: negative Cryoglobulin: negative C3: Low, C4: normal	NA	HCQ 200 mg/day, prednisolone 30 mg/day	NA	NA

Abbreviations: AIHA, autoimmune hemolytic anemia; ANCA, antineutrophil cytoplasmic antibodies; Anti-dsDNA, Anti-double stranded DNA; BMZ, basement membrane zone; C, complement; DIF, direct immunofluorescence; F, female; HCQ, hydroxychloroquine; H&E, hematoxylin and eosin stain; ICIs, immune checkpoint inhibitors; IU/mL, International Unit/mL; M, male; MKD, mg/kg/day; mo, months; NA, not available; NSCLC, non-small cell lung cancer.

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