Apremilast in refractory orogenital ulcers and other manifestations of Behçet's disease. National multicenter study of 51 cases in clinical practice.

Abstract Background Oral and/or genital aphthous ulcers are the most common symptoms of Behçet´s disease (BD), and are often refractory to conventional treatment. The inhibitor of phosphodiesterase-4 apremilast (APR) has demonstrated efficacy in the treatment of this manifestations. The objective of the present study was to assess the efficacy of APR in the management of refractory oral and/or genital ulcers in patients with BD. Methods National multicenter open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. Results We included 51 patients (35 women/16 men; mean age 44.7 ± 13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n = 19) or genital (n = 2) aphthous ulcers or both (n = 30). Other manifestations found at APR onset were arthralgia/arthritis (n = 16), folliculitis/pseudofolliculitis (n = 14), erythema nodosum (n = 3), furunculosis (n = 2), paradoxical psoriasis induced by TNFα-inhibitors (n = 2), ileitis (n = 2), deep venous thrombosis (n = 2), leg ulcers (n = 1), erythematosus and scaly skin lesions (n = 1), fever (n = 1), unilateral anterior uveitis (n = 1) and neurobehçet (n = 1). After a mean follow-up of 8.5 ± 6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. Conclusion APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

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FRI0487 APREMILAST IN MONOTHERAPY OR COMBINED IN NON-ULCER MANIFESTATIONS OF BEHÇET’S DISEASE. NATIONAL MULTICENTER STUDY OF 34 REFRACTORY CASES OF CLINICAL PRACTICE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4720 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 841.1-842

Author(s):

A. Herrero Morant ◽

B. Atienza Mateo ◽

J. Loricera ◽

V. Calvo del Rio ◽

J. L. Martín-Varillas ◽

...

Keyword(s):

Standard Dose ◽

Clinical Manifestations ◽

Skin Lesions ◽

Research Support ◽

Open Label ◽

Biologic Dmards ◽

Aphthous Ulcers ◽

Musculoskeletal Manifestations ◽

Del Rio

Background:Apremilast (APR) has demonstrated efficacy in orogenital ulcers of Behçet´s disease (BD). Response of other clinical manifestations remains unknown.Objectives:To assess the efficacy and safety of APR in monotherapy or combined with disease-modifying anti-rheumatic drugs (DMARDs) in non-aphthous ulcers of BD.Methods:National multicenter open-label study on 34 BD patients treated with APR at maintained standard dose of 30 mg twice daily.Results:From a cohort of 51 patients with APR by refractory orogenital ulcers of BD, we selected 34 (24 women/10 men, mean age 43.8±14.3 years), cases with another clinical manifestation/s.Excluding CTs, colchicine or NSAIDs, APR was given in monotherapy (n=21) or combined with conventional and/or biologic DMARDs in 13 cases (5 methotrexate, 3 azathioprine, 3 hydroxychloroquine, 1 sulfasalazine, 1 dapsone, 2 tocilizumab, 1 IFX). Other active manifestations present at APR onset were: arthralgia/arthritis (16, true arthritis in 5), folliculitis/pseudofolliculitis (14), erythema nodosum (3), furunculosis (2), paradoxical psoriasis by TNFi (2), intestinal ileitis (2), deep venous thrombosis (2), leg ulcers (1), erythematosus and scaly skin lesions (1), fever (1), unilateral anterior uveitis (1) and neurobehçet (1).After a median follow-up of 6 [3-12] months, folliculitis and ileitis improved, neurobehçet remained stable and musculoskeletal manifestations evolved in a variable way.(TABLE)TABLE.Conclusion:In addition of orogenital ulcers, APR in monotherapy or combined, seems to be useful in skin manifestations of BDDisclosure of Interests:Alba Herrero Morant: None declared, Belen Atienza Mateo: None declared, J. Loricera: None declared, Vanesa Calvo del Rio Grant/research support from: MSD and Roche, Speakers bureau: Abbott, Lilly, Celgene, Grünenthal, UCB Pharma, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Janssen and Celgene, Speakers bureau: Pfizer and Lilly, Gerard Espinosa: None declared, Jenaro Graña: None declared, Clara Moriano: None declared, Trinidad Pérez Sandoval: None declared, Manuel Martín Martínez: None declared, Elvira Diez: None declared, María Dolores García-Armario: None declared, Esperanza Martínez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Patricia Moya Alvarado: None declared, Francisca Sivera: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Isabel de la Morena: None declared, Francisco Ortiz Sanjuán: None declared, José Andrés Román Ivorra: None declared, Ana Pérez Gómez: None declared, Alejandro Olive: None declared, Carolina Díez: None declared, Juan José Alegre: None declared, D Ybáñez-García Speakers bureau: Lilly, Roche, Sanofi, Ángels Martínez-Ferrer: None declared, Javier Narvaez: None declared, Ignasi Figueras: None declared, Ana Isabel Turrión: None declared, Susana Romero-Yuste: None declared, Pilar Trénor: None declared, Soledad Ojeda Speakers bureau: AMGEN, LILLY, GEBRO, Miguel Á. González-Gay Grant/research support from: AbbVie, MSD and Roche, Speakers bureau: AbbVie, MSD and Roche, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD

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New coronavirus infection (COVID-19): from the dermatologist’s view

Annals of the Russian academy of medical sciences ◽

10.15690/vramn1359 ◽

2020 ◽

Vol 75 (4) ◽

pp. 292-299

Author(s):

Olga Yu. Olisova ◽

Ekaterina M. Anpilogova

Keyword(s):

Biologic Therapy ◽

Skin Lesions ◽

Mechanisms Of Action ◽

Published Data ◽

Erythematous Rash ◽

Biologic Drugs ◽

Cutaneous Manifestations ◽

Phosphodiesterase 4 ◽

Phosphodiesterase 4 Inhibitors ◽

Coronavirus Infection

Recently published data on the pathogenesis and cutaneous manifestations of a new coronavirus infection (COVID-19) are presented. The most described lesions are urticarial, papulo-vesicular, erythematous rash, purpura, livedo-angiitis, as well as chilblains. Eruptions mainly appear together with main COVID-19 symptoms or a few days later. The treatment of new coronavirus infection may lead to a quick regression of skin lesions along with improvement of the general state of the patient. The review also provides data on the fact that COVID-19 patients with severe psoriasis and atopic dermatitis receiving biologic therapy (guselkumab, ustekinumab, adalimumab, secukinumab, ixekizumab, etanercept, dupilumab) and phosphodiesterase-4 inhibitors experience mild or asymptomatic COVID-19. Moreover, such patients do not develop cutaneous manifestations of COVID-19. The specific COVID-19 treatment has not been developed yet. We think that these findings might provide better understanding of mechanisms of action of biologic drugs in COVID-19.

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Scabies: A Neglected Global Disease

Current Pediatric Reviews ◽

10.2174/1573396315666190717114131 ◽

2020 ◽

Vol 16 (1) ◽

pp. 33-42 ◽

Cited By ~ 1

Author(s):

Alexander K.C. Leung ◽

Joseph M. Lam ◽

Kin F. Leong

Keyword(s):

English Language ◽

Clinical Manifestations ◽

Skin Lesions ◽

Sarcoptes Scabiei ◽

Clinical Findings ◽

Effective Control ◽

Search Term ◽

Skin Contact ◽

Intense Pruritus ◽

Meta Analyses

Background: Scabies is a skin disease caused by an obligate human parasite mite Sarcoptes scabiei var. hominis. Children under the age of two and elderly individuals are at the greatest risk. Knowledge of this condition is important for an early diagnosis to be made and treatment to be initiated. Objective: The review aimed to familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of scabies. Methods: A search was conducted using Pubmed with the built-in "Clinical Queries" tool. The search term "Scabies" was used. The categories of "epidemiology", "diagnosis", "therapy", "prevention" and "prognosis" had a limited scope for primary clinical studies. Meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews were included. Only papers published in the English language were included. A descriptive, narrative synthesis was provided of the retrieved articles. Results: Worldwide, scabies affects 200 to 300 million individuals annually. The average prevalence is estimated to be 5 to 10% in children of developing countries. Transmission usually occurs after close prolonged skin-to-skin contact. Classic scabies is characterized by an erythematous papular eruption, serpiginous burrows, and intense pruritus. Sites of predilection include the webs of the fingers, volar wrists, lateral aspects of fingers, extensor surfaces of elbows and knees, waist, navel, abdomen, buttocks, groins, and, genitals. A clinical diagnosis of classic scabies can be made on the basis of the history and clinical findings. Other clinical variants include crusted scabies, nodular scabies, and bullous scabies. Finding the mite, ova, or fecal pellets on microscopic examination of scrapings taken from skin lesions confirms the diagnosis of scabies infestation. For eradication of scabies mites, the drugs of choice are topical permethrin and oral ivermectin. Conclusion: Scabies is a highly contagious parasitic cutaneous disease that is stigmatising and debilitating. Increased awareness, accurate diagnosis, and prompt treatment are essential for the effective control of scabies and for the prevention of the spread of the disease.

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Birt–Hogg–Dubé syndrome in Chinese patients: a literature review of 120 families

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01848-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Xiaowen Hu ◽

Guofeng Zhang ◽

Xianmeng Chen ◽

Kai-Feng Xu

Keyword(s):

Spontaneous Pneumothorax ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Lower Lobe ◽

Skin Lesions ◽

Jiangsu Province ◽

Chinese Patients ◽

Renal Tumors ◽

Pulmonary Cysts ◽

Exon 11

Abstract Objective To clarify the epidemiological and clinical features of Birt–Hogg–Dubé syndrome (BHDS) in Chinese patients. Methods We identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2008 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded. Results Twenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0 ± 13.9 years (range, 18–84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1–6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%). Conclusions Although BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

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766. Everything Old is New Again-A Case Series of New World Leishmaniasis in African Children in Portland, Maine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.956 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S428-S428

Author(s):

Jennifer Jubulis ◽

Amanda Goddard ◽

Elizabeth Seiverling ◽

Marc Kimball ◽

Carol A McCarthy

Keyword(s):

Latin America ◽

Cutaneous Leishmaniasis ◽

New World ◽

Pediatric Patients ◽

Data Extraction ◽

Clinical Manifestations ◽

Case Series ◽

Surgical Excision ◽

Skin Lesions ◽

Travel History

Abstract Background Leishmaniasis has many clinical manifestations and treatment regimens, dependent on species and host. Old world leishmaniasis is found primarily in Africa and Asia, and is associated with visceral disease, while new world disease, seen primarily in Latin America, is more commonly mucocutaneous. We present a case series of pediatric African patients with New World cutaneous leishmaniasis (NWCL). Methods Data extraction was performed via chart review, analyzing travel history, clinical presentation, diagnosis, and management in children with cutaneous leishmaniasis presenting to the pediatric infectious diseases clinic in Portland, ME. Biopsy specimens were sent to the federal CDC for identification by PCR and culture. Results Five cases of NWCL were diagnosed in pediatric patients in Maine from November 2018 through February 2020. Median age of patients was 10 years (range 1.5-15 years). Four cases (80%) occurred in children from Angola or Democratic Republic of Congo, arriving in Maine via Central/South America, with one case in a child from Rwanda who arrived in Maine via Texas. Three patients had multiple skin lesions and two had isolated facial lesions. Leishmaniasis was not initially suspected resulting in median time to diagnosis of 5 months (range 1-7 months). Four patients were initially treated with antibacterials for cellulitis and one was treated with griseofulvin. After no improvement, patients underwent biopsy with 2 patients diagnosed with L panamensis, 1 with L braziliensis, 1 with mixed infection (L panamensis and L mexicana), and 1 with Leishmania species only. One patient was managed with surgical excision, 3 with ketoconazole, and 1 was observed off therapy. Four patients were referred to otolaryngology. All continue to be followed in infectious disease clinic. Conclusion We present five cases of new world cutaneous leishmaniasis in African pediatric patients arriving to Maine through Latin America or Texas. Patients were diagnosed with cellulitis, tinea corporis or atopic dermatitis initially, underscoring importance of high index of suspicion in migrant patients. Detailed travel history and epidemiologic knowledge is essential to diagnosis, as patients may present with illness not congruent with country of origin. Optimal therapy remains unclear. Disclosures All Authors: No reported disclosures

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Inflammatory Skin Lesions in Three SARS-CoV-2 Swab-Negative Adolescents: A Possible COVID-19 Sneaky Manifestation?

Pediatric Reports ◽

10.3390/pediatric13020025 ◽

2021 ◽

Vol 13 (2) ◽

pp. 181-188

Author(s):

Giuseppe Ingravallo ◽

Francesco Mazzotta ◽

Leonardo Resta ◽

Sara Sablone ◽

Gerardo Cazzato ◽

...

Keyword(s):

Electron Microscopy ◽

Respiratory Symptoms ◽

Clinical Manifestations ◽

Skin Lesions ◽

Sweat Glands ◽

Histological Findings ◽

Immune Mediated ◽

Nodular Lesions ◽

Immunohistochemical Evidence ◽

Eccrine Sweat Glands

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with various clinical manifestations, including skin lesions. In particular, during the COVID-19 pandemic lock-down period numerous chilblain-like lesions, mainly located on the feet, were observed in adolescents. The latter were often asymptomatic or associated with very mild respiratory symptoms. Here, we report three cases of acral nodular lesions in SARS-CoV-2 swab-negative adolescents with histological findings of chronic immune-mediated inflammation and immunohistochemical evidence of SARS-CoV-2 spike glycoproteins in endothelial cells and eccrine sweat glands. In one of these cases, the virus presence was confirmed by electron microscopy.

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Enteropathic acrodermatitis in children

Voprosy dietologii ◽

10.20953/2224-5448-2021-2-21-28 ◽

2021 ◽

Vol 11 (2) ◽

pp. 21-28

Author(s):

V.P. Novikova ◽

◽

A.A. Pokhlebkina ◽

D.V. Zaslavsky ◽

A.I. Khavkin ◽

...

Keyword(s):

Zinc Deficiency ◽

Topical Therapy ◽

Clinical Manifestations ◽

Skin Lesions ◽

Knee Joints ◽

Zinc Metabolism ◽

Plasma Zinc ◽

Significant Treatment ◽

Zinc Concentrations ◽

Erythematous Plaques

Enteropathic acrodermatitis is a rare hereditary form of zinc deficiency, characterized by periorial and acral dermatitis, alopecia and diarrhea. Refers to congenital disorders of zinc metabolism, inherited as an autosomal recessive disease resulting from mutations in the gene for the zinc transporter SLC39A4. The prevalence ranges from 1 to 9:1,000,000, with an overall incidence of 1:500,000 newborns. The disease usually manifests itself in infancy, within a few weeks of stopping breastfeeding and switching the baby to a cow's milk-based formula, or in the first days of life if artificially fed from birth. The classical clinical manifestations of acrodermatitis enteropathic are characterized by the triad: acral and periofital dermatitis, alopecia and diarrhea, but all three signs together occur only in 20% of cases. Diarrhea may develop concurrently with skin symptoms, may precede or occur later. Characteristic signs of skin lesions include sharply demarcated, dry, scaly erythematous plaques or edematous foci with vesicles and pustules on the skin of the elbow and knee joints, distal extremities, genitals, in the inguinal folds, which are usually symmetrically distributed, have sharp boundaries and irregular outlines. The course of the skin syndrome is long, as it progresses, non-healing erosive and ulcerative areas appear. Plasma zinc deficiency is the gold standard for diagnosis. Most infants with AE have low plasma zinc concentrations (<500 mcg/L or <50 mcg/dl), but a level of less than 70 mcg/L on an empty stomach or less than 65 mcg/dl in older non-dieting children is considered diagnostically significant. Treatment for this disease usually includes enteral or parenteral zinc administration, at a dose of 1-3 mg/kg/day. for elemental zinc. A clinical response is observed within 5–10 days. Supportive zinc therapy is necessary throughout the patient's life, although periods of remission have been reported. Topical therapy is also used: Dexpanthenol in the form of a cream, applied 3 times a day in the area of dermatitis, can enhance re-epithelialization. There is no significant evidence of improvement with topical zinc application. No activity restrictions are required for patients with acrodermatitis enteropathic. Key words: zinc deficiency, enteropathic acrodermatitis, children

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CTIM-14. RANDOMIZED PHASE II OPEN LABEL STUDY OF NIVOLUMAB PLUS STANDARD DOSE BEVACIZUMAB VS NIVOLUMAB PLUS LOW DOSE BEVACIZUMAB IN RECURRENT GLIOBLASTOMA (RGBM). NIVOLUMAB BENEFITS OLDER POPULATION

Neuro-Oncology ◽

10.1093/neuonc/noab196.206 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi52-vi52

Author(s):

Manmeet Ahluwalia ◽

David Peereboom ◽

Yasmeen Rauf ◽

Patrick Wen ◽

David Reardon

Keyword(s):

Overall Survival ◽

Low Dose ◽

Standard Dose ◽

Performance Status ◽

Methylation Status ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Dose Effect ◽

Open Label ◽

Anti Vegf

Abstract BACKGROUND Approaches using anti-PD1 therapy alone in rGBM is of limited efficacy. VEGF is upregulated proangiogenic growth factor in GBM that contributes to tumor-associated immunosuppression. Preclinical data suggests a potential dose effect of anti-VEGF therapy on immunomodulation. Hence, a combination of anti-PD1 and anti-VEGF may be a promising approach in rGBM. METHODS 90 patients with GBM at first recurrence were randomized (1:1) to nivolumab (240 mg IV Q2 weeks) with bevacizumab at standard (10 mg/kg; Arm A) or at low dose (3 mg/kg; Arm B) IV Q2 weeks. Stratification included extent of resection, age, performance status and MGMT methylation status. Progression-free survival (PFS) and overall survival (OS) were compared between two arms. RESULTS 90 patients (Median age 60.6 years ranged 27.4-86.4, 67.8% male, median KPS 80) were enrolled between May 2018 and Jan 2020. Patients were followed in median 7.7 months (Range 0.7, 28.2). 35 patients were MGMT methylated and 53 patients were MGMT not hypermethylated and 2 were indeterminate. Overall Survival was not significantly different between arm A and arm B (1 year: 41.1 vs 37.7%, p=0.14), while OS was better for arm A in age > 60 (At 1-year: 46.2% vs 23.8%; Median: 10.6 vs 5.9 months; P=0.046). OS was no different in the two arms for age ≤ 60 years (At 1-year: 35.6% vs 56.4; Median 8.0 vs 12.4 months; P=0.90). Most frequent toxicities ( >20%) included fatigue (45.6%), proteinuria (34.4 %), diarrhea (28.9%), hypertension (23.3%) and lipase increase (21.1%). Toxicities in grade 3-4 were hypertension (7.8%), fatigue (5.6) and other non-neurological toxicities including DVT, PE, infection, and abnormal liver function. CONCLUSIONS Overall PFS and OS rates appear similar for nivolumab with either standard or low-dose bevacizumab compared to historical benchmarks of bevacizumab monotherapy. Nivolumab with standard bevacizumab seem to benefit patients older than 60 years old.

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Birt-Hogg-Dubé Syndrome in Chinese Patients: A Literature Review of 120 Families

10.21203/rs.3.rs-247951/v1 ◽

2021 ◽

Author(s):

Guofeng Zhang ◽

Xianmeng Chen ◽

Kaifeng Xu ◽

Xiaowen Hu

Keyword(s):

Spontaneous Pneumothorax ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Lower Lobe ◽

Skin Lesions ◽

Jiangsu Province ◽

Chinese Patients ◽

Renal Tumors ◽

Pulmonary Cysts ◽

Exon 11

Abstract ObjectiveTo clarify the epidemiological and clinical features of Birt-Hogg-Dubé syndrome (BHDS) in Chinese patients. MethodsWe identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2006 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded. ResultsTwenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0±13.9 years (range, 18-84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1-6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%).ConclusionsAlthough BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

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Impact of valganciclovir therapy on severe IRIS-Kaposi Sarcoma mortality: an open-label, parallel, randomized controlled trial.

10.1101/2021.10.24.21265453 ◽

2021 ◽

Author(s):

Patricia Volkow ◽

Leslie Chavez-Galan ◽

Lucero Ramon-Luing ◽

Judith Cruz-Velazquez ◽

Patricia Cornejo-Juarez ◽

...

Keyword(s):

Controlled Trial ◽

Kaposi Sarcoma ◽

Pulmonary Involvement ◽

Skin Lesions ◽

Attributable Mortality ◽

Control Group ◽

Open Label ◽

Parallel Group ◽

Pulmonary Lymph Node ◽

The Difference

High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with severe Immune reconstitution inflammatory syndrome (S-IRIS-KS), which can occur after initiating cART, and is linked with high mortality particularly in patients with pulmonary involvement. We investigate if valganciclovir initiated before cART decreases HHV-8 VL and assess if it reduces the incidence of S-IRIS-KS and its attributable mortality. Methods: Open-label parallel-group randomized clinical trial in AIDS cART naive patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node or gastrointestinal involvement, lymphedema, or equal or more 30 skin lesions. In the experimental group (EG), patients were randomized to valganciclovir 900 mg BID four weeks before cART and continued until week-48; in the control group (CG), cART was initiated on week-0. Non-severe-IRIS-KS was defined as: increase in the number of lesions plus equal or more than one log10 HIV-VL decrease or equal or more than 50 cells/mm3 increase or equal or more than 2-fold rise in baseline CD4+ cells. S-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia. Results: 40 patients were randomized and 37 completed the study. In the ITT analysis, the overall mortality did not differ between groups. In the per-protocol analyses, the difference showed a trend for higher S-IRIS-KS mortality in the CG 3/19 (15.7%), compared to EG 0/18 (p=0.07). The incidence of S-IRIS KS was significantly lower in the EG; two patients, one each had S-IRIS-KS episode (0.038 per 100 patient-days) compared to CG group, four patients developed 12 S-IRIS-KS episodes (0.21 per 100 patient-days); incidence rate of 0.09 (95% CI 0.02-0.5 p=0.006). Mortality in patients with pulmonary KS was significantly lower in EG, 3/4 in CG vs 0/5 in EG. S-IRIS-KS was associated with higher HHV-8-VL; IL6 and CRP; valganciclovir was protective. Of survivors at week 48, 82% achieved more than 80% remission. No difference was found between groups in the number of non-S-IRIS-KS events. Conclusions: Valganciclovir significantly reduced the episodes of S-IRIS-KS although attributable KS mortality was lower in the EG the difference was not significant (p=0.07). Mortality was significantly lower in EG patients with pulmonary KS.

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