Stephen J. Lockwood

Update on biologic safety for patients with psoriasis during pregnancy

Biologic agents have become more common to treat patients with psoriasis, but concerns about their effect on pregnancy and lactation often preclude this treatment during these time periods. During the past decade, we have gained a much better understanding of the course of psoriasis during pregnancy and the safety of the use of biologic agents during pregnancy and lactation. Under certain circumstances, biologic agents can be considered appropriate treatment options for patients who are pregnant or lactating.

Risk of Developing Pyoderma Gangrenosum after Procedures in Patients with a Known History of Pyoderma Gangrenosum – A Retrospective Analysis

Background The risk of postoperative pyoderma gangrenosum (PG) in patients with a known history of PG is unknown. Objective To quantify risk and identify patient‐ and/or procedure‐related risk factors for postsurgical recurrence or exacerbation of PG in patients with a known history of PG. Methods We retrospectively evaluated the likelihood of postsurgical recurrence or exacerbation of PG for all patients with a confirmed diagnosis of PG at Brigham and Womens Hospital and Massachusetts General Hospital from 2000 to 2015. Results In all, 5.5% of procedures (n = 33) led to recurrence of PG in 15.1% of patients (n = 25). Compared with skin biopsy, small open surgical procedures had an adjusted odds ratio (aOR) of 8.65 (95% confidence interval [CI], 1.55‐48.33) for PG recurrence or exacerbation; large open surgical procedures had an aOR of 5.97 (95% CI, 1.70‐21.00); and Mohs micrographic surgery/skin excision had an aOR of 6.47 (95% CI, 1.77‐23.61). PG chronically present at the time of the procedure had an aOR of 4.58 (95% CI, 1.72‐12.22). Immunosuppression, time elapsed since the original PG diagnosis, and procedure location did not significantly influence risk. Limitations Our study is limited by its retrospective nature and relatively small sample size. Conclusion There is a small but clinically meaningful risk for postsurgical recurrence or exacerbation of PG in patients with a known history of PG; higher risks occur with more invasive procedures and chronically present PG.

Adverse Reactions to Biologics in Psoriasis

Psoriasis is a chronic autoimmune disease which affects millions of people worldwide. Not only can psoriasis itself be debilitating and significantly reduce an individuals quality of life, but it is also a risk factor for other systemic disorders, such as metabolic syndrome, cardiovascular disease, and malignancy. Tremendous strides were made in the treatment of psoriasis during the mid-to-late-20th century, including the emergence of topical corticosteroids and vitamin D analogs, methotrexate, systemic retinoids, and phototherapy. However, it was not until 2004 with the advent of systemic biologic agents, which precisely target components of the immune system involved in the pathophysiological process of psoriasis, that the primary treatment benchmark increased from 50% improvement in the Psoriasis Area and Severity Index (PASI 50) to PASI 75, PASI 90, and even PASI 100, or complete resolution of cutaneous disease. Today, many patients receiving biologic therapy routinely experience greater than 75% or 90% reduction in cutaneous disease burden and a significant improvement in overall quality of life. These biologic agents are generally well-tolerated and safe but, like any medication, have associated adverse effects, some of which are predictable based on the effects of immune modulation, animal model studies, and human populations with known cytokine deficiencies. Going forward, it will be important to carefully monitor the safety profiles of these agents in both clinical trials and post-marketing surveillance registries to ensure long-term safety. It is reassuring that large safety registries are consistent in demonstrating an improved safety profile with newer and emerging biologic therapies.

A pilot study comparing histological and immunophenotypic patterns in stage 4 skin graft versus host disease from toxic epidermal necrolysis

Stage 4 skin graft‐versus‐host disease (GVHD) is associated with poor prognosis and high mortality rates. Clinical and histologic similarities with toxic epidermal necrolysis (TEN) make it difficult to distinguish between these 2 life‐threatening conditions.

The Association of Age With Clinical Presentation and Comorbidities of Pyoderma Gangrenosum

Importance Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis. Current knowledge of this rare disease is limited owing to a lack of validated diagnostic criteria and large population studies. Objective To evaluate the association of age with the clinical presentation and comorbidities of pyoderma gangrenosum. Design, Setting, and Participants This was a multicenter retrospective cohort study performed at tertiary academic referral centers in urban settings. Adults (≥18 years) who were evaluated and diagnosed as having pyoderma gangrenosum at the Brigham and Women’s and Massachusetts General Hospitals from 2000 to 2015 and the University of Pennsylvania Health System from 2006 to 2016 were included. Main Outcomes and Measures Patient demographics, clinical features, medical comorbidities, and treatment. Results Of the 356 validated cases of pyoderma gangrenosum included in the study, 267 (75%) were women and 284 (84.8%) were white. The mean (SD) age at presentation was 51.6 (17.7) years. Pathergy was recorded in 100 patients (28.1%). A total of 238 patients (66.9%) had associated medical comorbidities: inflammatory bowel disease in 146 patients (41.0%); inflammatory arthritis in 73 patients (20.5%); solid organ malignant neoplasms in 23 patients (6.5%); hematologic malignant neoplasms in 21 patients (5.9%); and hematologic disorders, specifically monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, and polycythemia vera in 17 patients (4.8%). When stratified by age, pathergy was more common in patients 65 years or older (36.3% vs 24.3%; P = .02). Inflammatory bowel disease was the only medical comorbidity that was more common in patients younger than 65 years (47.7% vs 26.6%; P < .001), while a number of medical comorbidities were more common in those 65 years or older, including rheumatoid arthritis (13.3% vs 6.2%; P = .03), ankylosing spondylitis (1.8% vs 0%; P = .04), solid organ malignant neoplasms (13.3% vs 3.3%; P < .001), hematologic malignant neoplasms (9.7% vs 4.1%; P = .04), and the aforementioned hematologic disorders (10.6% vs 2.1%; P < .001). Conclusions and Relevance Although clinical presentation in this large cohort was similar between different age groups, disease associations varied by age. The findings of this study may allow for a more focused, age-specific evaluation of patients with pyoderma gangrenosum.

The validity of the diagnostic code for pyoderma gangrenosum in an electronic database

Pyoderma gangrenosum (PG) is a rare inflammatory and ulcerative neutrophilic dermatosis with an estimated incidence of 3-10 cases per million people annually.1 Given that our understanding of PG is limited by disease rarity and considerable misdiagnosis rates (~30-50%),2 establishing a method to identify cases in large databases would facilitate population-based research. This approach has been used in other dermatologic diseases,3-6 where case identification is performed by diagnosis-related queries based on the International Classification of Diseases (ICD) code. This article is protected by copyright. All rights reserved.

Cutaneous Reactions to Drugs

Adverse drug reactions are a common problem for both outpatient and inpatient physicians. Usually, cutaneous manifestations are the first to be noticed by patients. Learning to recognize these reactions in their early form may prevent morbidity and mortality. A detailed history and physical examination are necessary to make the correct diagnosis and to identify the drug culprit. The primary morphology of skin lesions is the most important in this regard. Urticaria, exanthema, desquamation, pigmentary deposition, alopecia, acneiform reactions and mucosal erythema are important features to be able to be recognize. Laboratory work-up may be necessary in order to evaluate the patient for systemic complications. Finally, when the diagnosis is in doubt, skin biopsy is recommended in order to identify the effector cell (neutrophil, lymphocyte, or eosinophil) most significant to the disease process. These findings may aid the clinician in choosing the most effective therapy.

Unerwünschte Wirkungen von Biologika bei Psoriasis

Psoriasis ist eine chronische Autoimmunerkrankung, von der weltweit Millionen Menschen betroffen sind. Die Erkrankung ist nicht nur für sich selbst genommen sehr belastend und kann die Lebensqualität verringern, sondern sie stellt auch einen Risikofaktor für weitere systemische Erkrankungen dar, z.B. metabolisches Syndrom, kardiovaskuläre und maligne Erkrankungen. In der Behandlung der Psoriasis wurden im mittleren bis späten 20. Jahrhundert bahnbrechende Fortschritte erzielt, unter anderem durch die Entwicklung von topischen Kortikosteroiden und Vitamin-D-Analoga sowie Methotrexat, systemischen Retinoiden und Phototherapie. Doch erst 2004, mit dem Aufkommen der Biologika - neuartiger systemischer biologischer Arzneimittel, die sehr spezifisch gegen bestimmte Zielstrukturen des Immunsystems gerichtet sind -, wurde das Ansprechen laut PASI (Psoriasis Area and Severity Index) als Maßstab für das Hauptziel der Behandlung von einer Verbesserung um 50% (PASI 50) auf PASI 75, PASI 90 und sogar PASI 100, d.h. die vollständige Rückbildung der Hautläsionen, angehoben. Heute erreichen viele Patienten mit einer Biologika-Therapie routinemäßig eine Verringerung der kutanen Krankheitslast um 75% oder 90% und eine signifikante Verbesserung ihrer Lebensqualität insgesamt. Biologika sind im Allgemeinen gut verträglich und sicher, doch wie jedes Arzneimittel sind auch sie mit unerwünschten Wirkungen assoziiert. Einige dieser unerwünschten Wirkungen können anhand von Effekten der Immunmodulation, von Tiermodellen sowie von menschlichen Populationen mit bekannten Zytokindefizienzen vorhergesagt werden. Im nächsten Schritt ist es wichtig, sowohl in klinischen Studien als auch in Registern zur Anwendungsbeobachtung die Sicherheitsprofile dieser Wirkstoffe sorgfältig zu überwachen, um die Langzeitsicherheit zu bestätigen. Erfreulicherweise bescheinigen die großen Sicherheitsregister den neu hinzugekommenen bzw. hinzukommenden Biologika ein verbessertes Sicherheitsprofil. Übersetzter Auszug aus Curr Probl Dermatol. Basel, Karger, 2018, vol 53, pp 1-14 (DOI: 10.1159/000478072)

IgA multiple myeloma in a patient with an IgG pemphigus foliaceus-like exanthem

While the link between paraneoplastic pemphigus (PNP) and malignancy is well documented, reports of other pemphigus variants in association with neoplasms are scarcer. Reports have linked either IgA pemphigus with IgA monoclonal gammopathy or IgG-mediated pemphigus with IgG monoclonal gammopathy. We present the unique co-occurrence of IgA kappa multiple myeloma (MM) and pemphigus foliaceus (PF), an IgGmediated subtype of pemphigus.

Politics, culture, and the legitimacy of disease: the case of Buerger’s disease

Thromboangiitis obliterans (TAO) or Buerger’s disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.