Lab-Based Culprit Drug Identification Methods for Cutaneous Drug Eruptions: A Scoping Review.

BACKGROUND: Identification of culprit drugs when managing cutaneous drug eruptions is essential. Causality assessment methods (CAMs) have been proposed, including lab-based techniques. However, no consensus guidelines exist. OBJECTIVES: To identify and map the functionality and feasibility of lab-based CAMs. METHODS: A scoping review was conducted to identify culprit drug identification methods. Publications on lab-based methods were analyzed. Medline, Embase, and Cochrane Central Register of Controlled Trials databases were searched. RESULTS: Twenty-five publications met inclusion criteria. Nine lab-based CAMs were studied, including lymphocyte transformation test, cytokine measurement (ELISpot, ELISA, beads array assay), modified IFN-É£ ELISpot, CellScan, histamine release, granzyme B-ELISpot, intracellular granulysin, lymphocyte toxicity assay, and HLA allele genotyping. Diagnostic accuracy was reported for 8/9 methods. Clinical assessment and operational algorithms were commonly used as validation benchmarks. Lab-based methods were assessed at different phases of a drug eruption including in the acute (18.1%), recovery (27.3%), acute and recovery (27.3%), or an unspecified phase (27.3%). Lymphocyte transformation test (specificity 30% to 100%, sensitivity 27% to 73%) and cytokine measurement (specificity 76% to 100%, sensitivity 20% to 84%) were the most common methods studied. CONCLUSIONS: Lab-based CAMs can be low-risk, effective, and complementary of clinical methods. High-quality studies are needed to adequately develop and validate these tools for clinical practice.

Methods for Identifying Culprit Drugs in Cutaneous Drug Eruptions: A Scoping Review.

BACKGROUND: Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines. OBJECTIVES: Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies. ELIGIBILITY CRITERIA: Peer-reviewed publications involving culprit drug identification methods. SOURCES OF EVIDENCE: Medline, Embase, and Cochrane Central Register of Controlled Trials. CHARTING METHODS: Registered PRISMA-ScR format protocol on Open Science Forum. RESULTS: In total, 109 studies and 26 reviews were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment. Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories. CONCLUSIONS: Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis.

Checklist for the Systemic Treatment of Psoriasis Using Biologics: A Delphi Study.

BACKGROUND: Despite the complexity of psoriasis treatment using biologic therapy, there does not exist a standardized synoptic reporting form for the initiation of this population. The purpose of this study was to use a modified Delphi approach to develop a standard checklist for the standardized documentation of patients receiving systemic biologic therapy for psoriasis. METHODS: A modified Delphi survey was conducted over 3 rounds (February 2017 through January 2018). An expert panel generated a 51-item checklist that was proposed to participants. Items were rated on an anchored 1-7 Likert scale. Consensus was defined apriori as ≥ 70% agreement by respondents. RESULTS: A total of 58, 17, and 18 dermatologists participated in 3 consecutive Delphi rounds, respectively. Only half of the dermatologists surveyed reported using a checklist for the management of psoriasis. The final checklist comprised 19, 5, 6, and 9 items pertaining to patient history; physical exam and history of systemic therapy; vaccinations; and lab investigations and bloodwork, respectively. CONCLUSIONS: Given the increasing availability and complexity of biologic agents for psoriasis treatment, there is a need to promote standardized documentation for this population. The Checklist for the Systemic Treatment of Psoriasis presents 38 items that should be considered when initiating patients with psoriasis on biologic therapy.

A Case of Cutaneous B-Cell Lymphoma in Longstanding Systemic Lupus Erythematosus.

BACKGROUND: The association between lymphoproliferative malignancies and autoimmune rheumatological diseases, such as systemic lupus erythematosus (SLE), remains of great interest. It is known that individuals with immune dysregulation also have an increased risk of lymphoma. OBJECTIVE: To report a case of primary cutaneous diffuse large B-cell lymphoma of the leg type associated with longstanding SLE, as well as to review the literature for similar cases. METHODS: A PubMed search was done using the following search terms: lupus and B-cell lymphoma. RESULTS: Although several studies show that non-Hodgkin lymphoma is significantly increased in SLE, there is currently no literature reporting specifically on the risk of primary cutaneous lymphomas in patients with SLE. CONCLUSION: Our report highlights the possibility that patients with autoimmune disease are at increased risk of not only the classic forms of non-Hodgkin lymphoma but also primary cutaneous B-cell lymphomas.

A Case of Scurvy-Uncommon Disease-Presenting as Panniculitis, Purpura, and Oligoarthritis.

IMPORTANCE: Scurvy remains prevalent in certain populations, including addicts, people of low socioeconomic status, and the severely malnourished. It classically presents as follicular hyperkeratosis and perifollicular hemorrhage of the lower extremities, as well as bleeding in other areas such as the gingiva and joints. This case presentation and literature review highlights the common pathophysiological findings associated with scurvy and current methods of diagnosis and treatment. OBSERVATION: The patient described in this case presented with sudden oligoarthritis and purpura of the lower extremities. Following progression of the patient's symptoms and a low vitamin C serum concentration, the patient was treated with vitamin C supplementation and dramatically improved. This was considered to be the result of an underlying vitamin C deficiency secondary to insufficient fruit and vegetable intake due to allergies. CONCLUSIONS AND RELEVANCE: This case highlights the importance of maintaining a high index of suspicion for scurvy in atypical presentations of purpura not better explained by another disease or in additional populations at high risk of vitamin C deficiency. Early diagnosis by either a primary care physician or dermatologist can expedite the treatment process and improve patient prognosis.

Granulomatous and systemic inflammatory reactions from tattoo ink: Case report and concise review.

Tattoo pigment can precipitate numerous inflammatory states, and granulomatous tattoo reactions are a diagnostically challenging form. The skin is the most common site of inflammation, but systemic inflammation can occur. Reactions to black tattoo ink have a broad differential of cutaneous and systemic conditions. Sarcoidosis is an important consideration because it is unclear whether it is a separate entity. Here we present a 31-year-old male who developed an inflammatory eruption where he had black tattoos. He also developed circular patches of scalp alopecia, monocular uveitis, and an enlarged axillary lymph node, initially thought to represent lymphoma. Tissue biopsy of the skin and lymph node revealed findings consistent with granulomatous tattoo reaction. Investigations for other diagnoses, including sarcoidosis, were negative. He was treated with systemic corticosteroids and then with topical corticosteroids and oral hydroxychloroquine. This case report demonstrates the diagnostic challenge associated with granulomatous tattoo ink reactions. Further studies are needed to improve characterization and management of this condition.

Piperacillin-tazobactam-induced drug hypersensitivity syndrome.

The drug hypersensitivity syndrome (DHS) is a rare but serious and potentially life-threatening reaction to common drugs in predisposed individuals. The syndrome is a triad of fever, skin eruption, and internal organ involvement. Prompt identification and discontinuation of the offending drug with symptomatic treatment of toxic effects is the mainstay of therapy for DHS.

Contact sensitivity in patients with leg ulcerations: a North American study.

OBJECTIVES: (1) To determine the prevalence of allergen sensitivity in patients with past or present leg ulcers in 2 North American study centers vs European study findings and the North American Contact Dermatitis Group (NACDG) database and (2) to delineate a standard battery of allergens for patch testing in North American patients that is representative of the newer dressings and wound care products. DESIGN: Fifty-four patients, with or without dermatitis, were prospectively entered in the study. The patients were patch tested to the NACDG standard series and a comprehensive supplemental series of 52 allergens. SETTING: Wound healing clinics at Boston University Roger Williams Medical Center and University of Ottawa. RESULTS: Sixty-three percent (n = 34) of patients had 1 or multiple positive patch test results, and 37% (n = 20) had no positive patch test result. The most common allergens were Myroxylon pereirae (balsam of Peru) (30% [16/54]), bacitracin (24% [13/54]), fragrance mix (20% [11/54]), wood tar mix (20% [11/54]), propylene glycol (14% [7/52]), neomycin sulfate (13% [7/54]), benzalkonium chloride (13% [7/54]), carba mix (11% [6/54]), nickel sulfate (11% [6/54]), and control gel hydrocolloid (11% [6/54]). CONCLUSIONS: Comparable to European study findings, there is a high incidence of positive patch test results in patients with past or present leg ulcerations. The incidences of the most common allergens in our patient population were higher than those seen in the NACDG, except for nickel. Using a modified leg ulcer series along with the standard NACDG series is important in evaluating patients with leg ulcers.

Acanthosis nigricans in Kabuki syndrome.

BACKGROUND: Acanthosis nigricans has been classified in different ways. All classifications depend on the clinical picture and the association with other conditions. OBJECTIVE: We report a case of acanthosis nigricans in a patient with Kabuki syndrome. This syndrome is characterized by five main manifestations: typical facial features, post natal growth deficiency, skeletal abnormalities, dermatoglyphic abnormalities, and mild to moderate mental retardation. CONCLUSION: Our case may suggest that acanthosis nigricans could be associated with Kabuki syndrome.