Perioperative Bleeding Associated With Ibrutinib in Dermatologic Surgery: A Case-Control Study.

BACKGROUND: Ibrutinib, an irreversible Bruton tyrosine kinase inhibitor, has been associated with an increased risk of bleeding. There is a paucity of data on the risk of bleeding in patients on ibrutinib undergoing dermatologic surgery. OBJECTIVE: To determine the frequency of bleeding complications associated with ibrutinib in patients undergoing dermatologic surgery. MATERIALS AND METHODS: A retrospective, single-center, case-control study of patients on ibrutinib undergoing skin surgery between January 2013 and March 2020 compared with sex, disease, and age-matched control patients undergoing cutaneous surgeries. RESULTS: A total of 75 surgeries performed on 37 case patients and 116 surgeries performed on 64 control patients were included. Ibrutinib was associated with a statistically significant increased rate of bleeding events (6/75 [8%] vs 1/116 [0.8%], p -value = .02). Compared with ibrutinib patients who did not have a bleeding event, those on ibrutinib who suffered bleeding were all men, older (mean age 82.7 vs 73.0, p -value= .01), and had lower mean platelet counts (104.0 vs 150.5 K/µL, p -value = .03). CONCLUSION: Ibrutinib may be associated with increased risk of bleeding in patients with hematologic malignancies, particularly older men with lower platelet levels and on multiple anticoagulants. Transient discontinuation of ibrutinib should be considered for dermatologic surgeries.

Kaposi sarcoma misdiagnosed as granuloma annulare: A case of mistaken identity.

The microscopic features of patch stage Kaposi sarcoma (KS) and interstitial granuloma annulare (GA) may be difficult to differentiate, because both may exhibit a subtle "busy" dermis due to infiltration of spindled cells between collagen bundles. The clinical distinction is particularly challenging in human immunodeficiency virus (HIV)-affected individuals, as the incidence of GA appears to be greater in the HIV-infected population. KS is the most common neoplasm in this population. Despite the significant decrease in the incidence of KS since the advent of highly active antiretroviral therapy (HAART), KS tends to occur with late onset and indolent progression in patients with preserved immune function and minimal viral load. We present a 47-year-old homosexual HIV-positive man, under virologic and immunologic control on long-term HAART therapy, with a 5-year history of progressive red-brown patches and plaques on the legs, feet, hands, and trunk. Prior skin biopsy specimens were interpreted as interstitial GA. Histopathology on new skin biopsy specimens along with review specimens supported the diagnosis of plaque and patch stages of KS, respectively, supported by immunohistochemical expression of human herpes virus-8 (HHV-8). This case underscores the importance of maintaining a high suspicion for KS in progressive, treatment-recalcitrant skin lesions, particularly in HIV-infected individuals.

Autoimmune progesterone dermatitis in the adolescent population.

BACKGROUND/OBJECTIVE: Autoimmune progesterone dermatitis (APD) is a rare autoimmune hypersensitivity reaction that occurs cyclically at the peak of endogenous progesterone production during the menstrual cycle in women. No study characterizing APD in the adolescent population is found; it appears likely to be underdiagnosed and undertreated. METHODS: A retrospective, single-center, review of all adolescent and pediatric patients (<20 years old at onset) with documented diagnosis of APD. RESULTS: Seventeen adolescent APD patients were included (mean age at diagnosis: 14.4 ± 2 years, mean interval of 13.6 ± 11.1 months between symptom onset and diagnosis). Twelve patients presented with urticaria, two with fixed drug eruption. Erythema multiforme, eczema, and recurrent aphthous stomatitis were present in one patient each. Exposure to exogenous progestin was present in two patients prior to disease onset. Progesterone skin test was performed in six patients with positive results in two. Fourteen patients received antihistamines and/or a topical corticosteroid. Combined oral contraceptives (COCs) were given to eleven patients, in seven via continuous daily dosing. Gonadotropin-releasing hormone agonist (GnRHa) was used in five, progesterone desensitization in four, omalizumab in two, and danazol in one patient. CONCLUSIONS: Adolescent APD is associated with a significant delay in diagnosis. The most common manifestation is urticaria. Exogenous exposure to progestins is uncommon in adolescent APD. Continuous COC, GnRHa, and progesterone desensitization have been used to control symptoms. Large, multicenter studies are required to better define, diagnose, and treat this under recognized condition among adolescent patients.

Autosomal recessive congenital ichthyosis: Genomic landscape and phenotypic spectrum in a cohort of 125 consanguineous families.

Autosomal recessive congenital ichthyosis (ARCI), a phenotypically heterogeneous group of non-syndromic Mendelian disorders of keratinization, is caused by mutations in as many as 13 distinct genes. We examined a cohort of 125 consanguineous families with ARCI for underlying genetic mutations. The patients' DNA was analyzed with a gene-targeted next generation sequencing panel comprising 38 ichthyosis associated genes. The interpretations of results of genomic data were assisted by genome-wide homozygosity mapping and transcriptome sequencing. Sequence data analysis identified biallelic mutations in 106 families out of a total of 125 (85%), most of them (102, 96.2%) being homozygous, reflecting consanguinity in these families. Among the 85 distinct mutations in 10 different genes, 45 (53%) were previously unreported. Phenotype-genotype correlations allowed assignment of specific genes in the majority of the families to a specific subtype of ARCI, lamellar ichthyosis (LI) versus congenital ichthyosiform erythroderma (CIE). Interestingly, mutations in several genes could give rise to an overlapping phenotype consistent with either LI or CIE. Also, this is the third report for SDR9C7 and SULT2B1, and fourth report for CERS3 mutations. Direct comparison of our results with previously published regional cohorts highlights the global mutation landscape of ARCI, however, population specific differences were noted.

Angina bullosa haemorrhagica-like lesions in pemphigus vulgaris.

BACKGROUND/OBJECTIVES: The aim of this study was to describe a previously unreported association of oral pemphigus vulgaris with short-lived blood-filled painless blisters resembling angina bullosa haemorrhagica (ABH). METHODS: A cross-sectional study of consecutive patients with Pemphigus vulgaris. All patients were examined for the presence of ABH-like lesions, and demographic, clinical and histopathological data were collected. Histopathological examination was performed when feasible. RESULTS: A total of 318 with pemphigus vulgaris were included (63.5% female, mean age: 46 years). ABH-like lesions were present in 82 (25.8%) patients, commonly observed in the buccal mucosa (47, 57.3%) followed by the palate (15, 18.3%). All patients had normal platelet counts with no evidence of bleeding diathesis. Biopsies of the ABH-like lesions showed suprabasal clefts in four of six samples. ABH-like lesions were significantly associated with partial remission of pemphigus vulgaris (47.5%, P = 0.002) and the use of intraoral steroids (P = 0.001, odds ratio: 5.9 [95% confidence interval: 2.5-13.6]). CONCLUSION: ABH-like lesions may represent a transient or abortive form of oral pemphigus vulgaris and tend to have a benign and self-limiting nature.

Unique Presentation of Orf Virus Infection in a Thermal-Burn Patient After Receiving an Autologous Skin Graft.

We describe a burn patient who developed skin lesions on her skin-graft harvest and skin-graft recipient (burn) sites. Orf virus infection was confirmed by a combination of diagnostic assays, including molecular tests, immunohistochemical analysis, pathologic analysis, and electron microscopy. DNA sequence analysis grouped this orf virus isolate among isolates from India. Although no definitive source of infection was determined from this case, this is the first reported case of orf virus infection in a skin graft harvest. Skin graft recipients with exposures to animals may be at risk for this viral infection.

Patch testing in Iranian children with allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis is a common disorder in adults and children alike and appears to be on the increase. The purpose of this study was to determine the sensitization trends in Iranian children with contact dermatitis. METHODS: The result of 109 patch tests performed using the 24 allergens of the European Standard Series in patients below 18 years old from September 2007 to March 2009 were recorded and analyzed. The tests were evaluated at 48 and 72 h after performing. RESULTS: The study population consisted of 72 (66.1 %) females and 37 (33.9 %) males. Hands were the most commonly affected anatomic site. In the final evaluation of the tests on day three, 51 (46.8 %) individuals showed a positive reaction to at least one allergen. Females were significantly more likely to show a positive response to at least one allergen (p-value = 0.031, odds ratio: 2.46). The most common allergens were nickel sulfate, cobalt, methylisothiazolinone, and colophony with 21 (19.3 %), 11 (10.1 %), 7 (6.4 %), and 6 (5.5 %) positive reactions, respectively. Contact allergy to nickel sulfate was more common in females than males (23.6 % vs. 10.8 %). There was no statistically significant relationship between personal or family history of atopy and a positive reaction to patch testing. The clinical and practical relevance were assessed for nickel and cobalt with a clinical current relevance in 11 (52.3 %) and 4 (36.4 %), respectively. CONCLUSIONS: Nickel sulfate, cobalt, methylisothiazolinone, and colophony are the most common allergens responsible for induction of allergic contact dermatitis in Iranian children and adolescents. Females tended to show more positive reactions to allergens.

Treatment of erosive oral lichen planus with methotrexate.

BACKGROUND AND OBJECTIVES: Erosive oral lichen planus (EOLP) is a chronic inflammatory disease of the oral mucosa causing significant pain and impairment of the quality of life. No immediate and definitive cure is available, especially in its chronic and most recalcitrant forms. The objective of this study was to evaluate the efficacy of methotrexate treatment in EOLP. PATIENTS AND METHODS: A prospective open trial of oral methotrexate 15 mg QWK in 18 patients with EOLP (clinically and histopathologically confirmed) unresponsive to at least one previous topical or systemic medication. DURATION: Twelve weeks followed by twelve weeks of follow-up. RESULTS: Partial response or better was achieved in 15 (83.3%) patients. A statistically significant reduction in Thongprasom scale score was observed (mean value 5 at baseline, 3.08 ± 1.11 at week 12, 2.94 ± 0.97 at week 24, P value < 0.001). A statistically significant reduction was noted in the pain visual analogue scale (mean value 6.55 ± 2.33 at baseline, 2.46 ± 2.18 at week 12, 2.29 ± 1.93 at week 24, P value < 0.001). Adverse events occurred in four (22.2%) patients, requiring discontinuation of treatment in one patient. CONCLUSION: Methotrexate is a valuable therapeutic option in longstanding recalcitrant EOLP, particularly with respect to the improvement of subjective symptoms. Randomized controlled trials are required.

Temporal course of avascular femoral head necrosis in patients with pemphigus vulgaris.

BACKGROUND AND OBJECTIVES: Pemphigus vulgaris (PV) is typically treated with systemic corticosteroids and immunosuppressive agents. Avascular necrosis (AVN) of the femoral head is a well-recognized major complication of corticosteroid therapy. The characteristics of this serious complication in PV remain unknown. PATIENTS AND METHODS: Uncontrolled, retrospective study of all PV-related AVN cases diagnosed at an Iranian autoimmune bullous disease clinic between 1985 and 2013. RESULTS: Of the 2,321 medical records of PV patients reviewed, 45 (1.93 %) cases showed femoral AVN, with 30 (66.7 %) individuals being male. The mean age at diagnosis of AVN was 47.4 ± 14.2 years. The mean interval between the diagnosis of PV and the onset of AVN was 25.3 ± 18.3 months. With the exception of eight cases (17.8 %), the majority of patients developed AVN within three years after the diagnosis of PV. The mean cumulative dose of prednisolone in patients with AVN was 13,115.8 ± 7041.1 mg. There was a strong correlation between the total prednisolone dose and the time of onset of AVN (p = 0.001). In patients with a history of alendronate intake, that interval was significantly shorter (p = 0.01). CONCLUSIONS: Occurring in about 2 % of patients, AVN is a serious complication of corticosteroid treatment in patients with PV, predominantly in the first three years of treatment. In individuals receiving higher doses of prednisolone, AVN tends to occur earlier.

Zeitlicher Verlauf der avaskulären Nekrose des Hüftkopfes bei Patienten mit Pemphigus vulgaris.

HINTERGRUND UND ZIELE: Pemphigus vulgaris (PV) wird in der Regel mit systemischen Corticosteroiden und Immunsuppressiva behandelt. Avaskuläre Nekrose (AVN) des Hüftkopfes ist eine gut bekannte schwerere Komplikation einer Corticosteroid-Therapie. Die Charakteristika dieser schweren Komplikation bei PV sind nach wie vor unbekannt. PATIENTEN UND METHODEN: Nicht kontrollierte, retrospektive Untersuchung aller PV-bedingten AVN-Fälle, die in einer iranischen Klinik für bullöse Autoimmunerkrankungen zwischen 1985 und 2013 diagnostiziert wurden. ERGEBNISSE: Anhand der Krankenakten von 2321 untersuchten PV-Patienten wurden 45 Fälle (1,93 %) von femoraler AVN identifiziert. Dreißig davon waren Männer. Das mittlere Alter bei der Diagnose der AVN betrug 47,4 ± 14,2 Jahre. Der mittlere Zeitraum zwischen der Diagnose des PV und dem Einsetzen der AVN lag bei 25,3 ± 18,3 Monaten. Mit Ausnahme von acht Fällen (17,8 %) setzte die AVN bei der Mehrheit der Patienten innerhalb von drei Jahren nach Diagnose des PV ein. Die mittlere kumulative Dosis von Prednisolon bei Patienten mit AVN betrug 13.115,8 ± 7041,1 mg. Zwischen der Prednisolon-Gesamtdosis und dem Zeitraum bis zum Einsetzen der AVN bestand eine starke Korrelation (p = 0,001). Bei Patienten mit Alendronateinnahme in der Vorgeschichte war dieser Zeitraum signifikant kürzer (p = 0,01). SCHLUSSFOLGERUNGEN: Die AVN ist eine schwere Komplikation einer Corticosteroid-Behandlung bei Patienten mit PV. Sie wird bei 2 % der Patienten beobachtet und tritt vor allem in den ersten drei Behandlungsjahren auf. Bei Patienten, die höhere Dosen von Prednisolon erhalten, setzt die AVN tendenziell früher ein.

Clinical applications of topical ivermectin in dermatology.

Ivermectin (IVM) is a broad-spectrum anti-parasitic drug with significant anti-inflammatory properties. The emergence of treatment resistance to lindane, permethrin, and possibly malathion complicates the global strategy for management of common parasitic skin diseases such as scabies and head lice. In this regard. IVM has been safely and effectively used in the treatment of these common human infestations. In addition, IVM may be useful in inflammatory cutaneous disorders such as papulopustular rosacea where demodex may play a role in pathogenesis. Herein, we review the current applications of topical IVM in dermatology.

Hydroa vacciniforme with eye involvement: report of two cases.

We herein report two patients with hydroa vacciniforme and concomitant ophthalmic involvement, primarily in the form of keratoconjunctivitis leading to corneal opacity. Awareness of this occasional manifestation may help to prevent severe complications.

Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of the mediastinum: A favourable response to treatment and review of the literature.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disorder that occurs in association with an underlying neoplasm. Inflammatory myofibroblastic tumour (IMT) is a rare low-grade sarcoma of fibroblasts and myofibroblasts associated with inflammatory cells, most commonly occurring in the lung. In this study, a case of PNP associated with IMT of the mediastinum is reported. The patient had a favourable outcome following surgical resection and treatment with a systemic steroid, azathioprine, and i.v. immunoglobulin. The occurrence of PNP with sarcomas, specifically IMT, is noteworthy although it is not well studied in the existing literature.

Pigmented purpura dermatosis and viral hepatitis: a case-control study.

Pigmented purpuric dermatosis (PPD) is characterized by petechial and pigmented macules on the lower limbs. The aetiology of PPD remains obscure. Some reports have suggested an association between PPD and hepatitis B or C infection. This prospective case-control study was designed to investigate the association of positive hepatitis B or C serology with PPD. A total of 60 PPD patients and 230 randomly selected controls were enrolled. Sera from all patients and controls were tested for liver function tests (LFT), hepatitis B surface antigen (HBS Ag), and hepatitis C virus antibody (HCV Ab). The prevalence of HBS Ag in patients with PPD and the controls was 3 per cent (5/60) and 4.3 per cent (10/230), respectively. The prevalence of HCV Ab was 1.7 per cent (1/60) and 1.3 per cent (3/230) among patients and controls, respectively. No statistically significant difference was noted in the prevalence of positive hepatitis B or C serology (P-values 0.73 and 0.58, respectively). No statistically significant difference in LFT was observed between the two groups. Therefore, the authors believe it is unlikely that HBV or HCV are directly involved in the pathogenesis of PPD.

Autoimmune progesterone dermatitis: a retrospective case series.

Autoimmune progesterone dermatitis (APD) is a rare hypersensitivity disorder characterized by recurring dermatologic manifestations during the luteal phase of the menstrual cycle in women. Well-defined clinical and diagnostic criteria, outcomes measurements, and standard treatments are lacking. Methods: We performed a single-institution retrospective review of adult patients (older than 20 years at the time of diagnosis) with APD. Results: Fourteen patients were included with mean age of clinical onset of 34.3 ± 7.7 (range 24-54) years. There was a delay of 3.9 ± 5.5 (range 0.4-20) years between the onset of disease symptoms and diagnosis. The onset of APD was after exposure to exogenous progesterone in 9 of 14 patients. Progesterone skin test was performed in 9 patients and 6 were positive. Patients frequently presented with urticaria (9/14, 64.3%) and dermatitis (4/14, 28.6%). Continuous combined oral contraceptives (4/14, 28.6%), gonadotropin-releasing hormone agonist (3/14, 21.4%), and hysterectomy with bilateral salpingo-oophorectomy (2/14, 14.3%) were the most common attempted treatments with reliable outcomes. Conclusions: APD is a rare disorder which lacks universal diagnostic measures and criteria, contributing to a significant delay in diagnosis. Large-scale multicenter studies are needed to develop accurate tests, establish diagnostic criteria, and define treatment outcomes.

Vaccine-associated paralytic poliomyelitis in immunodeficient children, Iran, 1995-2008.

To determine the prevalence of vaccine-associated paralytic poliomyelitis (VAPP) in immunodeficient infants, we reviewed all documented cases caused by immunodeficiency-associated vaccine-derived polioviruses in Iran from 1995 through 2008. Changing to an inactivated polio vaccine vaccination schedule and introduction of screening of neonates for immunodeficiencies could reduce the risk for VAPP infection.

Lived Experiences of Patients Suffering from Acute Old World Cutaneous Leishmaniasis: A Qualitative Content Analysis Study from Iran.

BACKGROUND: The aim of this study was to explore the experiences of patients who suffer from acute cutaneous leishmaniasis in Iran, focusing on quality of life. METHODS: The study was conducted at two different sites in Iran in 2010-2011. Individual in-depth interviews were conducted with six men and six women parasitologically confirmed acute cutaneous leishmaniasis. Interviews were recorded, transcribed verbatim, and translated into English. Qualitative content analysis was used for data analysis. RESULTS: The participants, aged 23 to 63yr, had mild to severe disease. Based on the analysis four main themes were developed. "Fearing an agonizing disease" reflects patients' experiences of disease development resulting in sadness and depression, "struggling to cope" and "taking on the blame" both illustrate how patients experience living with the disease, which included both felt and enacted stigma as major social concerns. "Longing for being seen and heard" refers to patients' experiences with healthcare as well as their expectations and demands from communities and healthcare to be involved in closing the knowledge and awareness gap. CONCLUSION: Mental and social dimensions of cutaneous leishmaniasis were complex and adversely affected patients' lives by causing psychological burden and limiting their social interactions. Health authorities have to plan programs to increase the disease awareness to prevent the existing stigma to improve patients' social condition and medical care.