Etanercept therapy for toxic epidermal necrolysis Paradisi, Andrea, MD; Abeni, Damiano, MD; Bergamo, Fabio, MD ...
Journal of the American Academy of Dermatology,
08/2014, Volume:
71, Issue:
2
Journal Article
Peer reviewed
Background Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. Objective To describe a case series of patients with TEN ...treated with a single dose of etanercept. Methods We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan–Meier method. Results All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. Limitations This is a small, uncontrolled case series. Conclusion These preliminary results suggest the possibility that tumor necrosis factor–alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found.
Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the ...underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.
Paraneoplastic pemphigus is a rare autoimmune skin disease that is always associated with a neoplasm. Usually, oral, skin, and mucosal lesions are the earliest manifestations shown by paraneoplastic ...pemphigus patients. The pathogenesis of paraneoplastic pemphigus is not yet completely understood, although some immunological aspects have been recently clarified. Because of its rarity, several diagnostic criteria have been proposed. Besides, several diagnostic procedures have been used for the diagnosis, including indirect immunofluorescence, direct immunofluorescence, and ELISA. We reviewed the most recent literature, searching on PubMed "paraneoplastic pemphigus". We included also papers in French, German, and Spanish. We found 613 papers for "paraneoplastic pemphigus". Among them, 169 were review papers. Because of its varying clinical features, paraneoplastic pemphigus still represents a challenge for clinicians. Furthermore, diagnosis and management of paraneoplastic pemphigus requires close collaboration between physicians, including dermatologist, oncologist, and otorhinolaryngologist.
Background Genetic findings suggesting a lower susceptibility to melanoma in patients with vitiligo are supported by recent clinical studies. Nonmelanoma skin cancer (NMSC) has also been studied, but ...mainly in small samples, and with conflicting results. Objective We sought to study the relative risk (RR) of melanoma and NMSC in patients with vitiligo compared with that in patients seen for vascular surgery. Methods The frequency of melanoma and NMSC was compared between patients with vitiligo and patients seen for vascular surgery. Occurrence of skin cancer was compared by computing RR and modeled using multiple logistic regression. Results Overall, the crude RR for melanoma was 0.24 (95% confidence interval CI 0.13-0.45) in patients with vitiligo compared with those with a nondermatologic condition (occurrence 1.1‰, 95% CI 0.5‰-2.0‰ in patients with vitiligo and occurrence 4.5‰, 95% CI 3.8‰-5.4‰ in the control cohort). The crude RR for NMSC was 0.19 (95% CI 0.14-0.17) and the occurrence was 3.8‰ (95% CI 2.7‰-5.2‰) among patients with vitiligo and 19.6‰ (95% CI 18.0‰-21.4‰) in control subjects. Patients with vitiligo who underwent phototherapy had a markedly higher risk of both cancers. Conclusions In our large study, patients with vitiligo have a decreased risk of developing skin neoplasms, even considering that a larger proportion in this patient group is exposed to higher levels of ultraviolet radiation.
Introduction
Immunotherapy has changed the management of patients with various types of malignancies (melanoma, renal, lung, and bladder cancers) but immune checkpoint inhibitors may be associated ...with several adverse events. Up to 20% of patients treated with immune checkpoint inhibitors may develop dermatological immune-related adverse events, mostly rashes and pruritus but rarely even bullous pemphigoid.
Case report
We report a case of an elderly patient with advanced non-small cell lung cancer in therapy with pembrolizumab, 200 mg/body every three weeks. After 26 cycles of therapy, the patient developed widespread itching and then after 28 cycles she developed strained blisters filled with serous fluids on predominantly erythematous skin with suspicious of bullous pemphigoid.
Management and outcome: Skin biopsy confirms bullous pemphigoid, so we decided to permanently discontinue therapy with pembrolizumab and the patient is currently on therapy with doxycycline, nicotinamide, and clobetasol propionate with good regression of symptoms and cutaneous lesions.
Discussion
In the literature, the first case of bullous pemphigoid induced by pembrolizumab has been described in 2015. On Pubmed, from 2015 to date, we have found 19 cases of bullous pemphigoid during pembrolizumab therapy but only three of them are related to non-small cell lung cancer, adding our patient we reach a total of 20 cases. It could be interesting to investigate if there is a specific relationship between the appearance of itching and the development of bullous pemphigoid.
Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such ...as anti-tumor necrosis factor agents. Recently, a role of the interleukin-23/T-helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult-onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult-onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15-month follow-up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first-line treatment for PRP patients refractory to conventional therapies.
Recently, several case-control studies demonstrated an association between gliptins and bullous pemphigoid (BP) occurrence. However, data on the clinical and immunologic features of ...gliptin-associated bullous pemphigoid (GABP) are controversial.
This study aimed to clinically and immunologically characterize a large cohort of GABP patients to get an insight into the pathophysiology of this emerging drug-induced variant of BP.
Seventy-four GABP patients were prospectively enrolled and characterized from 9 different Italian dermatology units between 2013 and 2020.
Our findings demonstrated the following in the GABP patients: (1) a noninflammatory phenotype, which is characterized by low amounts of circulating and skin-infiltrating eosinophils, is frequently found; (2) immunoglobulin (Ig)G, IgE, and IgA humoral responses to BP180 and BP230 antigens are reduced in frequency and titers compared with those in patients with idiopathic BP; (3) IgG reactivity targets multiple BP180 epitopes other than noncollagenous region 16A.
A limitation of the study is that the control group did not comprise only type 2 diabetes mellitus patients with BP.
GABP patients show peculiar features of anti-BP180 and -BP230 humoral responses, laying the foundation for diagnostic improvements and getting novel insights into understanding the mechanism of BP onset.
Autoimmune response to cutaneous basement membrane components superimposed on a genetic skin fragility disease, hereditary epidermolysis bullosa (EB), has been described, but its effects on disease ...course remain unclear. We report a 69-year-old individual with congenital skin fragility and acral trauma-induced blistering that had suddenly worsened with the onset of severe itch and diffuse spontaneous inflammatory blisters. Next-generation sequencing identified compound heterozygous null and missense
COL7A1
mutations, allowing the diagnosis of recessive dystrophic EB. However, the patient’s clinical history prompted us to investigate whether he might have developed a pathological autoimmune response against basement membrane components. Tissue-bound and circulating IgG antibodies to the major bullous pemphigoid (BP) antigen, BP180, were detected in the patient’s skin and serum, respectively, consistent with a diagnosis of BP. Corticosteroid therapy was initiated resulting in remission of BP manifestations. EB patients presenting rapid disease worsening should be investigated for the development of a concomitant autoimmune blistering disease.
COVID-19 is characterized by a severe pulmonary disease due to severe acute respiratory syndrome (SARS)-CoV-2 infection. For clinicians involved in the management of patients with chronic autoimmune ...diseases the risk linked to the conditions itself and to drug-induced immunosuppression during the COVID-19 pandemic is a major topic. Pemphigus is a rare autoimmune blistering disease (AIBD) of the skin and mucous membranes caused by autoantibodies to desmosomal components, desmoglein 1 and 3. Among immunosuppressant therapies, rituximab (RTX) is considered a highly effective treatment with a favorable safety profile, but it induces a prolonged B-cell depletion that can lead to higher susceptibility to infections. For this reason, concerns about its use during the pandemic have been raised. We describe a case of a pemphigus patient in which RTX-induced B cell depletion led to the severe inflammatory phase, whereas corticosteroid treatment allowed a favorable outcome.
PDF
