Severe Skin Disorders Due to Sorafenib Use After Nivolumab Treatment in Renal Cell Carcinoma Patients.

BACKGROUND: We report two cases in which severe skin disorders developed during sorafenib treatment in patients with renal cell carcinoma (RCC) who had previously received nivolumab. CASE REPORT: Case 1: A 50-year-old man with RCC received nivolumab as the fifth-line therapy followed by sorafenib as the sixth-line therapy. On day 15 of sorafenib administration, the patient was hospitalized with systemic erythema multiforme, acne-like skin rash, and hand-foot syndrome. Case 2: A 40-year-old man with RCC received nivolumab as the second-line therapy followed by sorafenib as the fifth-line treatment. On day 12 of sorafenib administration, the patient was hospitalized with an acne-like skin rash and hand-foot syndrome. The skin disorders in the two cases improved within 2-3 weeks after sorafenib discontinuation and the start of treatment with topical and oral steroids. CONCLUSION: When using sorafenib in patients previously treated with nivolumab, close attention should be paid to the onset of serious skin disorders.

Vogt-Koyanagi-Harada Disease-Like Uveitis during Nivolumab (Anti-PD-1 Antibody) Treatment for Metastatic Cutaneous Malignant Melanoma.

Nivolumab is an anti-programmed cell death protein 1 monoclonal antibody that is used to treat metastatic cutaneous malignant melanoma. Although bilateral uveitis has been reported as a side effect of nivolumab administration, there are few reports of Vogt-Koyanagi-Harada disease (VKH)-like uveitis. We report such a case. A 63-year-old woman with metastatic cutaneous malignant melanoma experienced visual loss in both eyes 10 days after her second nivolumab injection. Her decimal best-corrected visual acuity (BCVA) was 0.7 in the right eye and 0.4 in the left eye. Examination revealed bilateral granulomatous keratic precipitates and posterior synechiae in the left eye. Optical coherence tomography showed multiple sites of serous retinal detachment (SRD) in the left eye and wavy retinal pigment epithelium in both eyes. Fluorescein angiography revealed multiple pinpoint-sized areas of leakage in both eyes and active leakage from the disc in her right eye. Indocyanine green angiography (IA) showed choroidal hyperfluorescence due to choroidal vascular leakage, with hypofluorescent dark spots during the late phase. These findings supported a diagnosis of VKH-like uveitis following nivolumab injections. Nivolumab was discontinued because of headache. Anterior chamber inflammation disappeared 3 weeks after starting topical corticosteroid treatment, and the SRD disappeared within 3 months. Her decimal BCVA recovered to 1.0 in the right eye and to 0.9 in the left eye. Also, the fluorescein angiography and IA findings had improved by 4 months. We concluded that careful follow-up is required after nivolumab treatment because VKH-like panuveitis might develop.

Cross-sectional survey on disease severity in Japanese patients with harlequin ichthyosis/ichthyosis: Syndromic forms and quality-of-life analysis in a subgroup.

BACKGROUND: Congenital ichthyoses (CIs) adversely affect quality of life (QOL) in patients. However, the effects of CIs on patient QOL have not been studied sufficiently. OBJECTIVE: To investigate the association between disease severity and QOL in patients with harlequin ichthyosis (HI) and ichthyosis: syndromic forms (ISFs) METHODS: Clinical information of patients with HI and ISFs from 2010 to 2015 were obtained from 100 dermatology departments/divisions of principal institutes/hospitals throughout Japan. We examined the relationship between disease severity and QOL in patients with HI and ISFs. Patients who were aged 8 years or older and participated in a multicenter retrospective questionnaire survey in Japan were assessed by dermatology life quality index (DLQI, range of 0-30) and clinical ichthyosis score (range of 0-100). RESULTS: Netherton syndrome patients had a significantly higher risk of allergy to food or environmental allergens than patients with other phenotypes. Keratitis-ichthyosis-deafness (KID) syndrome patients showed a significantly higher risk of skin infections than patients with other phenotypes. Complete data on DLQI were obtained from 13 patients, whose median age was 21 (8-71) years. Nine patients were male, and 4 were female. Systemic retinoids were administrated to 2 of the 3 HI patients. The Spearman's correlation coefficient between the clinical ichthyosis score and DLQI was 0.611 (P < 0.05). CONCLUSION: We confirmed that Netherton syndrome and KID syndrome patients have a higher risk of allergy to food or environmental allergens and of skin infections, respectively. QOL impairment correlates with disease severity in HI and ISFs patients.

Four cases of acute infectious urticaria showing significant elevation of plasma D-dimer level.

D-dimer, a fibrinolytic end-product, has been regarded as a biomarker indicating the severity of urticaria, especially in chronic urticaria. Regarding acute urticaria, D-dimer level is also suggested to be elevated, which may be significant in comparison with chronic urticaria. However, the clinical features of acute urticaria with concomitant significant elevation of D-dimer level have not been investigated in detail so far. We present four cases of acute urticaria fulfilling the proposed diagnostic criterion of acute infectious urticaria, in which significant elevation of D-dimer level and rapid spontaneous normalization in parallel with the resolution of fever and urticaria occurs. No cases had deep vein thrombosis, disseminated intravascular coagulation and malignancy. All cases responded well to antihistaminic treatment in combination with antibiotics, and their fever and urticaria resolved within 10 days. All cases showed severe wheals persistent for several days resolving with hyperpigmentation. Histologically, infiltration into blood vessel walls and interstitial infiltration of lymphocytes and polymorphonuclear cells were marked in the dermis. In our cases, clinical features accorded with acute infectious urticaria, and their histological features were similar to those of neutrophilic urticaria as described previously. In conclusion, there is a certain group of acute urticaria associated with significant elevation of D-dimer level. These common features of our cases may be characteristic in acute urticaria showing the coagulative and fibrinolytic abnormalities.

A case of dermatomyositis with esophageal fistula in whom blind mucosal biopsy detected occult oropharyngeal carcinoma.

We present a case of anti-transcription intermediary factor 1 (anti-TIF-1) antibody-positive dermatomyositis with concomitant esophageal fistula and extensive truncal erythema. The characteristic cutaneous features and presence of anti-TIF-1 antibodies were predictive for internal malignancy. However, repeated examinations for internal malignancy showed none, and blind mucosal biopsy was needed to diagnose oropharyngeal carcinoma. We should note the possibility of occult nasopharyngeal carcinoma and consider performing blind mucosal biopsy in dermatomyositis with esophageal fistula, especially with extensive truncal erythema.

Hyperkeratotic variant of porokeratosis Mibelli with dermal amyloid deposits.

We report a case of hyperkeratotic variant of porokeratosis Mibelli with dermal amyloid deposits. A 66-year-old man presented with multiple brownish keratotic lesions on the lower extremities, a verrucous nodule on the third toe of the left foot and brownish verrucous plaques on the buttocks for several years. Histopathological examination of the hyperkeratotic plaque in the right gluteal region revealed extreme hyperkeratosis and cornoid lamella. In the papillary dermis, there were prominent eosinophilic amorphous materials which were positive to Dylon staining. Treatment with oral etretinate resulted in a remission of the skin lesions in this case.