Temporal shifts of the microbiome associated with antibiotic treatment of purpuric drug eruptions related to epidermal growth factor receptor inhibitors.

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are selective and effective treatments for cancers with relevant mutations. Purpuric drug eruptions are an uncommon but clinically significant dermatological side effect related to EGFR inhibitor use that are associated with positive bacterial cultures and responsive to antibiotic treatment. However, the longitudinal temporal shifts in the skin microbiome that occur before and after antibiotic treatment of purpuric drug eruptions remain largely unknown. OBJECTIVES: To characterize temporal changes in the skin and mucosal microbiomes before and after antibiotic treatment of EGFR inhibitor-related purpuric drug eruptions. METHODS: Twelve patients who experienced EGFR inhibitor-related purpuric drug eruptions were recruited from a dermato-oncology clinic in Taiwan from May 2017 to April 2018. Swabs were obtained from skin lesions and the nasal mucosa before and after antibiotic treatment of purpuric drug eruptions. After the amplification and sequencing of bacterial 16S rRNA genes, the diversity and compositions of microbiomes sampled at different time points were compared. RESULTS: The alpha diversity (represented by the Shannon index) of the skin microbiome increased significantly in the recovered phase of purpuric drug eruptions compared with that of the active phase. By contrast, the nasal microbiome showed no significant change in alpha diversity. The relative abundance of Staphylococcus significantly decreased in samples from skin of the recovered phase, which was confirmed by analysis of compositions of microbiomes (ANCOM) and the ALDEx2 analysis packages in R. CONCLUSIONS: The cutaneous microbiome of purpuric drug eruptions showed a significant increase in alpha diversity and a decrease in the relative abundance of Staphylococcus following antibiotic treatment. These findings may help guide antimicrobial therapy of this EGFR inhibitor-related condition.

Clinical, Histopathologic, and Immunohistochemical Features of Patients with IgG/IgA Pemphigus.

Pemphigus is an autoantibody-mediated blistering disease. In addition to conventional pemphigus vulgaris and pemphigus foliaceus, several other types have been reported. Among them, IgG/IgA pemphigus is less well defined and seldom reported. To characterize the clinical, histopathologic, and immunohistochemical presentation of IgG/IgA pemphigus, we retrospectively identified 22 patients with the disease at a referral center in Taiwan. These patients showed two types of skin lesion: annular or arciform erythemas with blisters or erosions (45.5%) and discrete erosions or blisters such as those in conventional pemphigus (54.5%). Mucosal involvement was found in 40.9%. Histopathologic analysis identified acantholysis (77.3%) and intra-epidermal aggregates of neutrophils (40.9%) and eosinophils (31.8%). Direct immunofluorescence studies showed IgG/IgA (100%) and C3 (81.8%) depositions in the intercellular space of the epidermis. In immunohistochemical staining, patients with IgG/IgA pemphigus demonstrated significantly higher levels of epidermal expression of interleukin-8 and matrix metalloproteinase-9 than those with conventional pemphigus (p < 0.05). In conclusion, although IgG/IgA pemphigus is heterogeneous in presentation, it shows characteristic features that are different from other forms of pemphigus and should be considered a distinct type of pemphigus.

Prevalence, clinical features and treatment pattern of patients with concurrent diagnoses of rheumatoid arthritis and psoriatic disease: results of a 14-year retrospective study in a tertiary referral center.

BACKGROUND: Multiple comorbidities, including rheumatoid arthritis (RA), have been reported to be associated with psoriasis. OBJECTIVE: This study aimed to determine the prevalence and the clinical features of RA among patients with psoriasis in a tertiary referral center. METHODS: Between January 2000 and December 2013, all patients coded with psoriatic disease (ICD-9 CM 696.0 OR ICD-9 CM696.1) and RA (ICD-9 CM 714.0) in a tertiary medical center were enrolled. RESULTS: There were 10,844 patients and 9073 patients with psoriatic disease and RA identified by diagnostic codes, respectively. Among patients with psoriasis, 111 patients had claim-based diagnosis of RA (1.02%). By reviewing medical records and telephone interview or clinic visits, 25 of the 111 patients (0.23%) was identified unequivocally as having concurrent RA. Among them, 17 (68%) were female and 16 (64%) patients developed arthritis prior to the onset of psoriasis with a mean lag of 6.3 years (1-19 years); 8 (32%) had psoriasis skin lesions prior to the onset of arthritis with a mean lag of 6.9 years (3-20 years); 1 (4%) had skin lesions and arthritis in the same time; 17 (68%) patients also fulfilled the CASPAR classification criteria for psoriatic arthritis. The mean age of onset for arthritis was 49.6 years old. CONCLUSIONS: The prevalence of RA in psoriasis might be overestimated in some previous studies using claimed database. Patients with concurrent RA and psoriasis showed a comparable age of onset and male to female ratio, but had more axial involvements compared to patients without psoriasis.

Safety Profile of Secukinumab in Treatment of Patients with Psoriasis and Concurrent Hepatitis B or C: A Multicentric Prospective Cohort Study.

Safety data for secukinumab in patients with psoriasis and viral hepatitis are lacking. The aim of this study is to investigate the risk of reactivation of hepatitis B virus (HBV)/hepatitis C virus (HCV) in patients with psoriasis who are receiving secukinumab therapy. This multicentre study screened 284 patients with psoriasis with available HBV and HCV serological data and 63 patients with concurrent HBV/HCV infection were enrolled. In the absence of antiviral prophylaxis, 7 of 46 (15.2%) patients with HBV exhibited HBV reactivation during secukinumab therapy. The risk of reactivation was significantly higher in HBsAg-positive patients, compared with HBsAg-negative/HBcAb-positive patients (24.0% vs. 4.17%, p = 0.047). One of 14 (7.1%) HCV patients showed enhanced replication of HCV with hepatitis. No virus reactivation occurred in patients receiving antiviral prophylaxis. HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients can develop virus reactivation during secukinumab therapy, thus necessitating close monitoring of viral load and considering an antiviral prophylaxis for all HBsAg-positive patients with psoriasis.

Purpuric Drug Eruptions Caused by Epidermal Growth Factor Receptor Inhibitors for Non-Small Cell Lung Cancer: A Clinicopathologic Study of 32 Cases.

Importance: Purpuric skin lesions have only rarely been reported in patients receiving epidermal growth factor receptor inhibitors. However, their clinical and histopathologic presentations have varied considerably. Objective: To characterize purpuric skin eruptions caused by epidermal growth factor receptor inhibitors. Design, Setting, and Participants: This prospective study enrolled 32 patients who presented to an integrated dermato-oncologic clinic in a tertiary referral medical center with purpuric skin lesions after using epidermal growth factor receptor inhibitors from January 1, 2013, through December 31, 2015. Exposures: Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, erlotinib, and afatinib. Main Outcomes and Measures: Clinical presentations, histopathologic features, laboratory examinations, and treatment outcomes of patients with purpuric drug eruptions. Results: Thirty-two patients, 14 with purpuric drug eruptions without pustules (mean [SD] age, 60 [11] years; 12 female and 2 male) and 18 with purpuric drug eruptions with pustules (mean [SD] age, 64 [11] years; 12 female and 6 male), were identified. The median time to development of skin lesions was 3.5 months. The clinical presentations were characterized by purpuric macules, papules, and confluent plaques predominantly on the lower extremities. Pustules in various sizes could be found in 18 patients (56%). Eleven patients (34%) had skin lesions that covered places other than the lower extremities. Eczema craquelé-like features developed in 13 patients (41%). Bacterial pathogens were frequently identified in these skin lesions. Among them, Staphylococcus aureus was the most predominant and was found in 20 patients (63%), commonly in those with cutaneous pustules. Epidermal dysmaturation, neutrophil exocytosis, perivascular infiltration of lymphocytes and neutrophils, red blood cell extravasation, and plumping endothelium were the main histopathologic features. The expressions of filaggrin and human ß-defensin 2 in lesional skin of these patients were markedly reduced. All patients improved after receiving at least 1 week of systemic antibiotic treatment; the doses of epidermal growth factor receptor inhibitors were also changed for 14 patients (44%). Conclusions and Relevance: Purpuric drug eruptions caused by epidermal growth factor receptor inhibitors are uncommon and have characteristic clinical and histopathologic presentations. The role of bacterial pathogens in this reaction is important and requires further exploration.

Long-term Sequelae of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions characterized by different extents of epidermal necrosis and mucosal breakdown. A limited number of studies have reported the long-term patterns of SJS and TEN complications in patient populations over long follow-up periods. The aim of this retrospective study was to collect data on long-term sequelae in patients admitted for SJS, SJS/TEN overlap, or TEN between 1998 and 2012. Among all 102 patients eligible for analysis, the 2 most common sequelae were cutaneous and ocular problems, both with incidences of 44.1%. Visceral organ involvement was observed in 2 patients with irreversible deterioration of chronic kidney disease and in one patient with interstitial lung disease. Autoimmune disease was present in 6 patients: Sjögren's syndrome or Sjögren-like syndrome in 5 patients and concomitant systemic lupus erythematosus and Hashimoto thyroiditis in one patient.

Liver injury in patients with DRESS: A clinical study of 72 cases.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a syndrome involving multiple systems. Liver injury is the most common visceral manifestation. OBJECTIVE: The purpose of this study was to investigate the types of liver injury and factors associated with DRESS. METHODS: A retrospective cohort study was conducted in Taiwan using a DRESS database compiled from December 2000 to March 2013. RESULTS: Seventy-two cases were included in this study. Among them, 62 (86.1%) cases involved liver injury, 6 of which (9.7%) were liver injury before skin presentation. The distribution of liver injury patterns at initial presentation was 23 cholestatic type (37.1%), 17 mixed type (27.4%), and 12 hepatocellular type (19.4%). Patients with hepatocellular-type injuries were younger, with a median age of 31.5 (P = .044). Individuals with liver function results more than 10 times the upper limit were more likely to have fever (P = .026), took more time to recover, and had fewer eosinophils in the dermis (P = .002). LIMITATIONS: The study was a retrospective cohort study with limited cases. CONCLUSIONS: Liver injury is common in DRESS and frequently associated with atypical lymphocytosis. The cholestatic type is the most common type. Patients with cholestatic-type injuries were older and more frequently had interface changes in skin pathology.