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 201825 | 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 201920 | 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 201924 | 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 201926 | 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 202022 | 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 201927 | 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 20219 | 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 202128 | 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.