Psoriasiform drug eruption secondary to sorafenib: case series and review of the literature.

The expanding use of novel targeted anticancer agents such as sorafenib has led to an increasing number of dermatologic adverse events. Although cutaneous adverse events are commonly described in patients taking sorafenib, there are few reports describing psoriasis secondary to this medication. In this report, we describe 3 patients with sorafenib-induced psoriasiform drug eruption and review the available literature of similar patient cases. Our findings highlight shared characteristics among affected patients and potential treatment options for patients in whom sorafenib cannot be discontinued. Increased awareness of such drug eruptions and management options is critical to prevent suboptimal dosing and decreased quality of life.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5-91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.

Tinea folliculorum complicating tinea of the glabrous skin: an important yet neglected entity.

Dermatophytes are capable of infecting the skin and its appendages such as nails and hairs producing a variety of clinical conditions. Hair invasion by dermatophytes is a key feature of tinea capitis and tinea barbae but not of tinea of glabrous skin. In this project, we studied the clinico-mycological aspects of follicular involvement in patients with dermatophytosis of the glabrous skin. In total, 16 patients, eight males and eight females, were included in the study. All were adults except for one girl. The disease durations ranged from one month to more than ten years. Fourteen (78.5%) had multiple lesions, and most of them had undergone treatment with antifungals, antibiotics, or steroids. Dermoscopic examination showed infected hairs in the form of broken stubs, coily, curly, or as black dots on the surface of the lesions. Pathogens were either anthropophilic (seven cases of Trichophyton rubrum) or zoophilic (six cases Microsporum canis, three cases of the T. mentagrophytes). Patients responded well to oral griseofulvin or terbinafine, and topical antifungals. No antifungal resistance developed during the treatment course. Follicular involvement of glabrous skin is not as rare as previously thought and should be considered for systemic antifungal treatments.

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.

Desmoplastic sebaceoma arising from nevus sebaceus: a new variant.

Nevus sebaceus is known to have the potential to develop into various secondary tumors. We observed a sebaceoma arising from a nevus sebaceus excised from the left cheek of a 51-year-old woman. This sebaceoma showed desmoplastic change similar to that observed in desmoplastic trichoepithelioma and desmoplastic trichilemmoma. This heretofore undescribed desmoplastic variant of sebaceoma should not be mistaken for invasive sebaceous carcinoma.

MafB promotes atherosclerosis by inhibiting foam-cell apoptosis.

MafB is a transcription factor that induces myelomonocytic differentiation. However, the precise role of MafB in the pathogenic function of macrophages has never been clarified. Here we demonstrate that MafB promotes hyperlipidemic atherosclerosis by suppressing foam-cell apoptosis. Our data show that MafB is predominantly expressed in foam cells found within atherosclerotic lesions, where MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM). In the absence of MafB, activated LXR/RXR fails to induce the expression of AIM, a protein that is normally responsible for protecting macrophages from apoptosis; thus, Mafb-deficient macrophages are prone to apoptosis. Haematopoietic reconstitution with Mafb-deficient fetal liver cells in recipient LDL receptor-deficient hyperlipidemic mice revealed accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. These findings represent the first evidence that the macrophage-affiliated MafB transcription factor participates in the acceleration of atherogenesis.

A rapidly recurring cutaneous xanthogranuloma-like histiocytic tumor: a diagnostic challenge.

Xanthogranuloma (XG) is a benign cutaneous histiocytic tumor occurring mainly in young children. Onset in adulthood is rarely observed. We encountered an unusual case of an XG-like cutaneous tumor on the scalp of a 50-year-old man. The tumor recurred with multiple satellite nodules soon after surgical excision. This unusual clinical behavior has not previously been described for XG and caused a diagnostic challenge; it was unclear whether the tumor was an atypical XG or a malignant dermal tumor mimicking an XG. Our analyses favored an XG-like dermal histiocytic tumor. A longer follow-up and reports of similar cases will reveal its true nature.

Clinicopathological study of Fox-Fordyce disease.

Fox-Fordyce disease (FFD) is a rare skin disease manifesting as multiple pruritic follicular papules involving the skin-bearing apocrine glands. Reports of FFD in Asian people are scant. In this retrospective study, we describe the clinicopathological findings of five cases of FFD affecting Taiwanese subjects. Clinically, all patients presented with numerous uniform, 2-3-mm, skin-colored to light brown, dome-shaped papules with smooth surface, which were distributed in the apocrine gland-containing areas. Pruritus varied from mild to severe. The histopathology is characterized by focal spongiosis in the upper infundibulum with perifollicular fibrosis and lymphohistiocytic infiltrate. FFD needs to be differentiated from lichen amyloidosis, Darier's disease, syringoma, lichen simplex chronicus and spongiotic dermatitis clinically or pathologically. The findings of focal spongiosis in upper infundibulum associated with a perifollicular lymphohistiocytic infiltrate can facilitate the diagnosis of FFD.