scholarly journals RASopathies: Dermatologists’ viewpoints

2021 ◽  
Vol 0 ◽  
pp. 1-12
Author(s):  
Aparna Palit ◽  
Arun C. Inamadar

Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome/loose anagen hair, Legius syndrome, Costello syndrome, cardio-facio-cutaneous syndrome and capillary malformation-arteriovenous malformation are the well-recognized RASopathies. These are characterized by multi-organ tumours and hamartomas. Some other features in common are facial dysmorphism, skeletal abnormalities, congenital heart disease, neurocognitive abnormalities and risk of various solid-organ and haematological malignancies. Some of the RASopathies are heterogeneous, caused by several gene mutations resulting in variations in phenotypes and severity ranging from mild to fatal. Significant phenotypic overlaps among different disorders, often makes it difficult to pinpoint a clinical diagnosis. Specific cutaneous manifestations are present in some of the RASopathies and are often the earliest clinical signs/symptoms. Hence, dermatologists contribute significantly as primary care physicians by identifying disorder-specific cutaneous lesions. However, diagnostic work-up and management of these disorders are often multidisciplinary. Confirmation of diagnosis is possible only by genetic mapping in each case. Genetic counseling of the patients and the affected families is an important component of the management. The aim of this review is description of cutaneous manifestations of RASopathies in the background of multi-system involvement to enable dermatologists a comprehensive and logical approach to work up and diagnose such patients in the absence of facility for specific molecular testing.

2021 ◽  
Vol 49 ◽  
Author(s):  
Isabel Rodrigues Rosado ◽  
Julia Perinotto Picelli ◽  
Juliana Gonzaga da Silva ◽  
Marina Cazarini Madeira ◽  
Taís Teixeira Zambarda ◽  
...  

Background: Systemic lupus erythematosus (SLE) is an immune-mediated and multisystemic disorder which etiology is believed to be multifactorial. Its clinical signs vary accordingly to affected organs, cutaneous lesions being the most frequently observed. There are few reports of SLE in dogs with neurological manifestations. Therefore, the aim of this report is to describe a case of SLE in a dog with indicative signs of nervous system involvement.Case: A 6-year-old Border Collie bitch was referred to the Veterinary Hospital (HVU) of the University of Uberaba (UNIUBE) with a history of  with cluster seizures, inappetence and urinary incontinence. Erythema and flaking of nasal plan were noted on physical examination, and splenomegaly on abdominal palpation. Thrombocytopenia and slightly increased ALT were found on blood tests. Ehrlichiosis was suspected and doxycycline was prescribed together with phenobarbital for the control of seizures. In the follow-up visit, the dog was still presenting urinary incontinence, thrombocytopenia and splenomegaly. Also, an ulcer on the nasal mucocutaneous junction was observed. The patient went through a neurological examination which indicated thalamocortical lesion. Cerebrospinal fluid samples were obtained for cytology, culture and canine distemper test, and serology tests for leishmaniasis, toxoplasmosis and neosporosis were done. No alterations were found in these exams. The histopathology of the nasal lesion was proceeded and showed results consistent with lupus erythematosus. It was prescribed a 15-day course of prednisolone at immunosuppressive dose. The patient showed clinical improvement with this treatment. Azathioprine was started along with gradual removal of prednisolone. After twenty days of discontinuation of this drug, the dog presented epileptic seizures, urinary incontinence, thrombocytopenia, increased ALT and worsened nasal lesion. Prednisolone at immunosuppressive dose was reintroduced and the dose of azathioprine, increased. One week past this, the patient showed inappetence and an extensive hematoma in the thoracic region. Lab exams confirmed drug-induced acute pancreatitis. All medications were interrupted, the patient was hospitalized, and treatment for pancreatitis was initiated, but the dog passed away.Discussion: For involving multiple body systems and for presenting varied clinical signs, diagnosing SLE can be challenging in clinical routine. The dog from this report was a Border Collie; this breed is considered to be predisposed to this disease. The animal had a history of being exposed to solar radiation for a large part of the day, had dyspigmentation of nasal plan and had no application of sunscreen, predisposing the occurrence of SLE. Neurological signs are uncommon in SLE, but the seizures and the urinary incontinence were the main reasons for the dog’s guardian to look for medical assistance. The suspicion for SLE was raised due to cutaneous manifestations and persistent thrombocytopenia along with splenomegaly. Histopathological findings are essential for diagnosing SLE, as well as antinuclear antibody tests. Nonetheless, due to financial limitations, this last test was not performed. Azathioprine is an immunomodulating drug largely used along with glucocorticoids when treating SLE; however, this medication is prone to induce side effects as the ones presented by the dog from this report. Therefore, it is concluded that SLE should be considered as a differential diagnosis in patients showing cutaneous, hematological, systemic and neurological manifestations, considering the variety of signs caused by this disorder.Keywords: seizures, dog, immune-mediated encephalopathy. Lúpus eritematoso sistêmico associado a manifestações neurológicas em cadela da raça Border CollieDescritores: crises epilépticas, cão, encefalopatia imunomediada.


2018 ◽  
Vol 5 (3) ◽  
pp. 86-90 ◽  
Author(s):  
Alison Haynes ◽  
Andrew O’Keefe ◽  
Paul Dancey ◽  
Kamal Ohson ◽  
Lesley Turner ◽  
...  

Background: Leukocyte adhesion deficiency (LAD) syndromes are primary immunodeficiency disorders caused by defects in adhesion molecules on leukocytes resulting in impaired migration into tissues. Common cutaneous manifestations of LAD include bacterial infections, omphalitis with delayed separation of the umbilical cord, impaired pus formation and poor wound healing. LAD is associated with significant morbidity and mortality, making early diagnosis and management integral in the care of these patients. Methods: Molecular testing and flow cytometry for expression of CD18 were performed on 2 siblings presenting with cutaneous lesions including pyoderma gangrenosum (PG). Results: We describe 2 siblings with a novel homozygous mutation in ITGB2 (c.2070del, p.Asp690Glufs*25) resulting in an atypical presentation of LAD-I with PG. Conclusion: LAD should be considered in patients presenting with unexplained PG, even in the absence of significant infections or umbilical cord complications. Statement of novelty: To the best of our knowledge, we describe a novel homozygous mutation in ITGB2 (c.2070del, p.Asp690Glufs*25) resulting in LAD-I. Patients with LAD-I may present with unexplained PG and may lack classic symptoms including umbilical cord complications.


2021 ◽  
Vol 9 ◽  
pp. 2050313X2199719
Author(s):  
Juan Carlos Palomo-Pérez ◽  
Maria Elisa Vega-Memije ◽  
David Aguilar-Blancas ◽  
Erik González-Martínez ◽  
Lucia Rangel-Gamboa

China officially recognized atypical pneumonia outbreak in December 2019; on 11 March 2020, the World Health Organization declared COVID-19 as a pandemic that is produced by a new coronavirus, named SARS-CoV-2, of rapid transmissibility, which can be asymptomatic, with mild to severe respiratory symptoms, and with cardiovascular, neurological, gastrointestinal, and cutaneous complications. Considering that the pandemic prolonged more than initially expected was prognostic, it is essential for the medical community to identify the signs and symptoms of COVID-19. Thus, this work’s objectives were to present cases of cutaneous lesions observed in COVID-19 Mexican patients. We register cutaneous lesions in COVID-19 patients referred from internal medicine and otorhinolaryngology services to dermatology. We presented four interesting cases with cutaneous lesions, including exanthema morbilliform, urticaria, chilblains, ecchymosis, and facial edema, and review the available literature. The most frequent cutaneous markers are rash, chilblains, and urticaria. Skin lesions may be the first manifestation of COVID-19, accompany initial respiratory symptoms, or appear during the disease course. Symptoms associated with vascular changes (livedo reticularis and vasculitis) are considered of poor prognosis.


2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Jihane Hamdi ◽  
Zahra Bamouh ◽  
Mohammed Jazouli ◽  
Meryem Alhyane ◽  
Najet Safini ◽  
...  

Abstract Background Goatpox is a viral disease caused by infection with goatpox virus (GTPV) of the genus Capripoxvirus, Poxviridae family. Capripoxviruses cause serious disease to livestock and contribute to huge economic losses. Goatpox and sheeppox are endemic to Africa, particularly north of the Equator, the Middle East and many parts of Asia. GTPV and sheeppox virus are considered host-specific; however, both strains can cause clinical disease in either goats or sheep with more severe disease in the homologous species and mild or sub-clinical infection in the other. Goatpox has never been reported in Morocco, Algeria or Tunisia despite the huge population of goats living in proximity with sheep in those countries. To evaluate the susceptibility and pathogenicity of indigenous North African goats to GTPV infection, we experimentally inoculated eight locally bred goats with a virulent Vietnamese isolate of GTPV. Two uninfected goats were kept as controls. Clinical examination was carried out daily and blood was sampled for virology and for investigating the antibody response. After necropsy, tissues were collected and assessed for viral DNA using real-time PCR. Results Following the experimental infection, all inoculated goats displayed clinical signs characteristic of goatpox including varying degrees of hyperthermia, loss of appetite, inactivity and cutaneous lesions. The infection severely affected three of the infected animals while moderate to mild disease was noticed in the remaining goats. A high antibody response was developed. High viral DNA loads were detected in skin crusts and nodules, and subcutaneous tissue at the injection site with cycle threshold (Ct) values ranging from 14.6 to 22.9, while lower viral loads were found in liver and lung (Ct = 35.7 and 35.1). The results confirmed subcutaneous tropism of the virus. Conclusion Clinical signs of goatpox were reproduced in indigenous North African goats and confirmed a high susceptibility of the North African goat breed to GTPV infection. A clinical scoring system is proposed that can be applied in GTPV vaccine efficacy studies.


2018 ◽  
Vol 46 (1) ◽  
pp. 7
Author(s):  
Francina Dos Santos Silva ◽  
Simone Carvalho dos Santos Cunha ◽  
Andrea Regina de Souza Baptista ◽  
Vivian Dos Santos Baptista ◽  
Kássia Valéria Gomes Coelho da Silva ◽  
...  

Background: Sporotrichosis is a zoonosis caused by fungi of the Sporothrix schenckii complex. Cats have important zoonotic potential due to the high parasite load found in the cutaneous lesions. Refractory cases to antifungal therapy are increasing, becoming a public health problem. Miltefosine is a drug with high in vitro activity against Sporothrix brasiliensis. However, this efficacy has not been confirmed in vivo yet and administration has not been studied in the feline species. This study aimed to evaluate the effectiveness and safety of miltefosine administration in cats with resistant sporotrichosis.Materials, Methods & Results: Ten cats with refractory sporotrichosis were included in this study. Inclusion criteria were previous diagnosis for sporotrichosis associated with therapy with oral antifungals (itraconazole and/or potassium iodide) for more than one year, followed by one of these conditions: incomplete clinical remission, worsening of disease during treatment or recurrence after conventional treatment. Cats underwent clinical and dermatological examinations. Data on lifestyle and previous treatments were provided by the owners. Fungal culture and histochemical techniques were performed in all cats before miltefosine treatment. Blood samples were collected before and during the study for laboratory tests, such as blood count, blood urea nitrogen (BUN), serum creatinine, alanine aminotransferase (ALT) and alkaline phosphatase, as well as serology for Feline Immunodeficiency (FIV) and Feline Leukemia (FeLV). Miltefosine was prescribed at a dosage of 2 mg/kg orally every 24 h. The animals were monitored by phone during the whole process and reassessed on days 0, 15, 30 and 45 of the treatment. Out of 10 cats, lesions were present on the nose in nine, ears in four, periocular areas in one and limbs in four. One cat received treatment for 45 days, six for 30 days, one for 21 days, one for 15 days and one for 3 days. One cat showed no response to the treatment and nine showed disease progression. Hyporexia and weight loss were the most frequent clinical signs related to miltefosine treatment, followed by sialorrhea, vomiting and diarrhea. Few adverse effects on hematology and biochemistry (mainly renal and hepatic parameters) were observed during the study. Hematocrit decrease was observed in four animals. However, only one cat had hematocrit decrease below normal values (anemia), which was already present before miltefosine administration. Other cats had a decrease of five points. Three cats showed elevation in leucometria and four in plasma protein. In relation to renal and hepatic biochemistry, one animal showed a BUN increase and another one showed a transient increase in ALT. Two animals started the treatment with increased ALT but had no problems during the study and values decreased even during the miltefosine administration.Discussion: Although two cats showed sialorrhea, most owners did not report difficulty in administering the drug orally, representing an advantage of this medication. Weight loss, secondary to gastrointestinal changes, was the most clinically relevant alteration. The most frequent hematological alteration was hematocrit decrease and only the animal that started the study with 20% hematocrit ended the study with anemia. Renal and hepatic parameters were not significant in the cats of this study. Miltefosine did not lead to sporotrichosis remission in this small population of cats, which reveals that, despite its in vitro efficacy against Sporothrix spp., the drug is not effective in vivo in the feline species. Further studies are needed to investigate the efficacy of this drug in a larger number of cats, and possible reasons for its in vivo ineffectiveness.


2021 ◽  
Vol 8 ◽  
Author(s):  
Christina M. Davy ◽  
Leonard Shirose ◽  
Doug Campbell ◽  
Rachel Dillon ◽  
Christina McKenzie ◽  
...  

Emerging infectious diseases (EIDs) are typically characterized by novelty (recent detection) and by increasing incidence, distribution, and/or pathogenicity. Ophidiomycosis, also called snake fungal disease, is caused by the fungus Ophidiomyces ophidiicola (formerly “ophiodiicola”). Ophidiomycosis has been characterized as an EID and as a potential threat to populations of Nearctic snakes, sparking over a decade of targeted research. However, the severity of this threat is unclear. We reviewed the available literature to quantify incidence and effects of ophidiomycosis in Nearctic snakes, and to evaluate whether the evidence supports the ongoing characterization of ophidiomycosis as an EID. Data from Canada remain scarce, so we supplemented the literature review with surveys for O. ophidiicola in the Canadian Great Lakes region. Peer-reviewed reports of clinical signs consistent with ophidiomycosis in free-ranging, Nearctic snakes date back to at least 1998, and retrospective molecular testing of samples extend the earliest confirmed record to 1986. Diagnostic criteria varied among publications (n = 33), confounding quantitative comparisons. Ophidiomycosis was diagnosed or suspected in 36/121 captive snakes and was fatal in over half of cases (66.7%). This result may implicate captivity-related stress as a risk factor for mortality from ophidiomycosis, but could also reflect reporting bias (i.e., infections are more likely to be detected in captive snakes, and severe cases are more likely to be reported). In contrast, ophidiomycosis was diagnosed or suspected in 441/2,384 free-ranging snakes, with mortality observed in 43 (9.8 %). Ophidiomycosis was only speculatively linked to population declines, and we found no evidence that the prevalence of the pathogen or disease increased over the past decade of targeted research. Supplemental surveys and molecular (qPCR) testing in Ontario, Canada detected O. ophidiicola on 76 of 657 free-ranging snakes sampled across ~136,000 km2. The pathogen was detected at most sites despite limited and haphazard sampling. No large-scale mortality was observed. Current evidence supports previous suggestions that the pathogen is a widespread, previously unrecognized endemic, rather than a novel pathogen. Ophidiomycosis may not pose an imminent threat to Nearctic snakes, but further research should investigate potential sublethal effects of ophidiomycosis such as altered reproductive success that could impact population growth, and explore whether shifting environmental conditions may alter host susceptibility.


2022 ◽  
Vol 11 (2) ◽  
pp. 375
Author(s):  
Magdalena Żychowska ◽  
Adam Reich

Background: (Video)dermoscopy is a non-invasive diagnostic technique that has a well-established role in dermatooncology. In recent years, this method has also been increasingly used in the assessment of inflammatory dermatoses. So far, little is known about the (video)dermoscopic features of dermatomyositis (DM). Methods: Consecutive patients with DM were included in the study and videodermoscopic assessments of the nailfolds, scalp, and active skin lesions were performed. Results: Fifteen patients with DM (10 women and 5 men) were included. Capillaroscopy showed elongated capillaries (90.9%), avascular areas (81.8%), disorganized vessel architecture (81.8%), tortuous capillaries (72.7%), dilated capillaries (72.7%), and hemorrhages (72.7%). The trichoscopic findings included linear branched vessels (80.0%), linear vessels (60.0%), linear curved vessels (53.3%), perifollicular pigmentation (40.0%), perifollicular erythema (33.3%), scaling (20.0%), white (20.0%) or yellow (20%) interfollicular scales, and white (20.0%) or pinkish (13.3%) structureless areas. Polymorphic vessels of an unspecific distribution and white or pink structureless areas were frequently observed under dermoscopy in cutaneous manifestations of DM, including Gottron’s papules and Gottron’s sign. Conclusions: Dermoscopy of the nailfolds (capillaroscopy), scalp (tricoscopy), and active cutaneous lesions may be of value in the preliminary diagnosis of DM.


2021 ◽  
Vol 12 ◽  
Author(s):  
Marcia M. L. Kho ◽  
Stefan Roest ◽  
Dominique M. Bovée ◽  
Herold J. Metselaar ◽  
Rogier A. S. Hoek ◽  
...  

BackgroundStudies on herpes zoster (HZ) incidence in solid organ transplant (SOT) recipients report widely varying numbers. We investigated HZ incidence, severity, and risk factors in recipients of four different SOTs, with a follow-up time of 6–14 years.MethodsRecords of 1,033 transplant recipients after first heart (HTx: n = 211), lung (LuTx: n = 121), liver (LiTx: n = 258) and kidney (KTx: n = 443) transplantation between 2000 and 2014 were analyzed for VZV-PCR, clinical signs of HZ, and complications.ResultsHZ was diagnosed in 108 of 1,033 patients (10.5%): 36 HTx, 17 LuTx, 15 LiTx, and 40 KTx recipients. Overall HZ incidence rate after HTx (30.7 cases/1,000 person–years (PY)), LuTx (38.8 cases/1,000 PY), LiTx (22.7 cases/1,000 PY) and KTx (14.5 cases/1,000 PY) was significantly higher than in the general 50–70 year population. Multivariable analysis demonstrated age ≥50 years at transplantation (p = 0.038, RR 1.536), type of organ transplant (overall p = 0.002; LuTx p = 0.393; RR 1.314; LiTx p = 0.011, RR 0.444; KTx p = 0.034, RR 0.575), CMV prophylaxis (p = 0.043, RR 0.631) and type of anti-rejection therapy (overall p = 0.020; methylprednisolone p = 0.008, RR 0.475; r-ATG p = 0.64, RR1.194) as significant risk factors. Complications occurred in 33 of 108 (31%) patients (39% of HTx, 47% of LuTx, 20% of LiTx, 20% of KTx): post-herpetic neuralgia, disseminated disease, and cranial nerve involvement.ConclusionHZ incidence and severity in SOT recipients are most pronounced after heart and lung transplantation, in older patients, and when CMV prophylaxis is lacking.


Author(s):  
Kirty Nahar ◽  
Usha Bohra ◽  
Vivek Arya

Androgenic alopecia is a patterned hair loss occurring due to systemic androgens and genetic factors. It is the most common cause of hair loss in both genders. The appearance of this condition is the cause of significant stress and psychological problems, making appropriate management important. A 68-year-old postmenopausal female presented with complaints of increased hair loss from scalp, excessive hair growth at undesired sites and hirsutism not corrected with medications. On thorough investigations, CT scan whole abdomen and endocrinological workup, a clinical diagnosis of alopecia and hirsutism due to hyperandrogenemia secondary to ovarian tumor made. Abdominal hysterectomy with B/L salpingo-oophorectomy was done. Histopathological examination revealed an encapsulated tumor in right ovary-sex cord stromal tumor consistent with Leydig cell tumor in right ovary, no evidence of malignancy. Left ovary was normal. Patient showed significant regression of clinical signs and symptoms on follow up after 1 month. All women with severe hirsutism or androgenic alopecia needs further work up to locate the source of androgen over production.


2018 ◽  
Vol 2018 ◽  
pp. 1-3
Author(s):  
Abbas Azadi ◽  
Payman Jafarpour Fard ◽  
Mohammad Almasian

Brucellosis is a disease that is transmitted from animals to humans mainly via the consumption of unpasteurized dairy products, and it can involve any organ all over the body. Here, we report a significant rare case of brucellosis with cutaneous manifestations in a 52-year-old male patient whose disease was diagnosed via a serology test. The patient received standard antibiotic treatment, and his cutaneous lesions healed quickly. Although the cutaneous manifestations of brucellosis are exceedingly rare, in case of encountering ulcerative lesions and other cutaneous findings, particularly in endemic areas, infection with brucellosis should be kept in mind as an important differential diagnosis.


Sign in / Sign up

Export Citation Format

Share Document