Multiple Skin Lesions Research Articles

A Case Report of Male Systemic Lupus Erythematous with Antinuclear Antibodies-Negative: A Challenging Diagnosis

Systemic lupus erythematosus (SLE) is a connective tissue disease of unknown etiology that predominantly affects women of childbearing age. We report a case of male systemic lupus erythematous with antinuclear antibodies and typical clinical presentations of multiple skin lesions, polyarticular joint pain, fatigue, anorexia, and hair loss. Full evaluations were used to establish a diagnosis of SLE. The lower prevalence of SLE among males and antinuclear antibody-negative patients poses a great challenge for diagnosis. Therefore, as primary care doctors, we need to have a high suspicion of systemic lupus erythematous even in male and antinuclear antibody-negative patients. Thus, early treatment may help patients improve their quality of life.

Multiple sebaceous tumors in a 58-year-old man with colorectal cancer.

The Muir‐Torre Syndrome is a rare genodermatosis, defined by the occurrence of sebaceous neoplasia and internal malignancies and caused by mutations in the mismatch repair gene. We describe the case of 58‐year‐old man who, over the course of several years, had multiple skin lesions and colon cancer. The syndrome was diagnosed using Sanger sequencing, which allowed us to find the causative mutation.

Linear immunoglobulin A bullous dermatosis with severe ocular and oropharyngeal involvement

Linear IgA bullous dermatosis (LABD) is a rare chronic autoimmune epidermal disorder that presents with bullous and vesicular lesions affecting the skin and, more rarely, oral and ocular mucosa.1 This report describes a previously well 74-year-old man on no medications who presented with 3 months of oral mucosal ulceration causing dysphagia and odynophagia, bilateral ocular irritation and injection, and 6 months of cutaneous lesions. Clinical examination revealed multiple papular erythematous skin lesions on the trunk and axilla.

Development and application of a sensitive droplet digital PCR for the detection of red mark syndrome infection in rainbow trout (Oncorhynchus mykiss)

Red Mark Syndrome (RMS) is a skin disease of uncertain etiology affecting farmed rainbow trout (Oncorhynchus mykiss). It consists of single or multiple skin lesions usually localized on the trunk of fish approaching market size.Studies showed as rickettsia-like organism (RLO), currently referred as Midichloria-like organism (MLO), is supposed to be involved in RMS.Midichloria-like has been identified consistently in RMS-affected fish. Its identification within skin and spleen has been possible through the use of PCR methods, including standard PCR, nested PCR and quantitative PCR (qPCR).Droplet digital PCR (ddPCR) is a relatively novel, sensitive, accurate and absolute quantification technique. Recent studies applied successfully this technique to infectious spleen and kidney necrosis virus (ISKNV) in teleosts, proving its superiority when compared to qPCR.The goal of the present study is to establish a sensitive ddPCR method to rapidly detect and quantify MLO DNA.We explored the feasibility of ddPCR to detect MLO from 40 rainbow trout spleen samples and compared the data with qPCR. The detection limit of the ddPCR was found to be 2.25 copy number, which is lower than the 36 copy number determined for TaqMan real-time PCR (qPCR). This indicated that the sensitivity of the ddPCR assay was one order of magnitude higher than the sensitivity of the qPCR assay. The detection results for fish samples showed that the positive detection rate of ddPCR (65%) was higher than that of qPCR (52.5%).The method used has revealed to be specific to MLO and does not cross-react with other fish bacterial DNA. The ddPCR method established in this study shows superiority for detection in minimal volume samples with low bacterial loads and may be used both as surveillance of possible transmission routes and potential sources.

Calcific Uremic Arteriolopathy or Calciphylaxis in a Hemodialysis Patient: Case Study and Review of the Literature

Calcific uremic arteriolopathy (CUA) is a rare pathology affecting 5% of dialysis patients but with a poor prognosis. It is characterized by calcification and thrombotic lesions of the microcirculation leading to hyperalgesic ischemic skin lesions. Several risk factors have been identified, mainly warfarin treatment, mineral and bone disorders (MBD), inflammation and malnutrition. In the evocative forms, the diagnosis is made based upon the physical examination finding of classic painful ulcerated lesions that are covered by a black eschar. Skin biopsy, due to the risk of aggravation and delayed healing, is only performed in case of doubt diagnosis. The therapeutic attitude due to the lack of solid randomized studies is based on expert consensus and requires a multidisciplinary approach. We report here the case of a patient with CUA revealed in the form of multiple ulcerative-necrotic skin lesions associated with pressure sores and arterial wounds.

Cutaneous metastasis of invasive ductal carcinoma on FNAC: A case report

The cutaneous metastasis is a late uncommon manifestation of cancer and indicates poor prognosis. The cutaneous metastasis can be a first presentation of underlying malignancy. The FNAC is an easy tool for rapid diagnosis of cutaneous metastasis. A 47-year-old female, known case of invasive ductal carcinoma presented to hospital with history of multiple nodular skin lesions over the body varying in size from 0.5-1.5 cm from past 2 months. The smears were cellular and comprises of loose clusters and singly scattered atypical epithelial cells, displaying moderate degree of pleomorphism with mild amount of cytoplasm, large irregular nucleus with fine to coarse chromatin, inconspicuous to conspicuous nucleoli and occasional atypical mitosis against a lipohemorrhagic background. The diagnosis of metastatic deposits of invasive ductal carcinoma was rendered. The clinical diagnosis of metastatic deposits can be challenges, especially in case of distant metastasis or when the cutaneous metastasis is the first presentation. The cutaneous metastasis can be confused clinically as adnexal lesion. The use of special stains and immunohistochemical markers can aid in diagnosis.

Changes in the microbiological diagnosis and epidemiology of cutaneous leishmaniasis in real-time PCR era: A six-year experience in a referral center in Barcelona.

BackgroundLeishmaniasis is a neglected disease caused by different species of the protozoa Leishmania spp. Cutaneous lesions are the most common clinical manifestation. This disease is prevalent in tropical and subtropical areas, including the Mediterranean basin. In Spain, Leishmania (L.) infantum is the only endemic species, but imported cases are often diagnosed. Different classical parasitological methods can be performed for cutaneous leishmaniasis (CL) diagnosis; but currently molecular techniques serve as a relevant tool for the detection and characterization of Leishmania parasites. We aimed to evaluate clinical and epidemiological characteristics of CL diagnosed patients by real-time PCR in a tertiary hospital over a six-year period.Methodology/Principal findingsClinical, epidemiological and microbiological data were retrospectively collected and analyzed. In our study, CL was confirmed in 59 (31.4%) out of 188 patients by real-time PCR, showing an increase over recent years: 11 cases of CL between 2014 and 2016 and 48 between 2017 and 2019. Real-time PCR was performed on skin swabs and/or biopsies samples, with a positivity of 38.5% and 26.5%, respectively. Results were 100% concordant when biopsy and skin swab were performed simultaneously. L. (L.) infantum was the most frequent species detected (50%), followed by L. (L.) major (45%) and Viannia subgenus (5%), which were detected only in imported cases. L. (L.) major was almost entirely detected in travelers/migrants from Morocco. Multiple and atypical skin lesions were more common in imported cases than in autochthonous cases (44.4% vs. 21.8%).Conclusions/SignificanceAn increase in both autochthonous and imported CL cases has been observed in past years in our hospital. Molecular techniques assist in improving CL diagnosis and characterization of the Leishmania species, mainly in imported cases.

Pityriasis Rosea Shortly After mRNA-1273 COVID-19 Vaccination

With the increase in rates of vaccination against COVID-19, various cutaneous reactions have been reported after vaccination, including pityriasis rosea (PR) (Catala et al., 2021Catala A Munoz-Santos C Galvan-Casas C Roncero Riesco M Revilla Nebreda D Sola-Truyols A et al.Cutaneous reactions after SARS-COV-2 vaccination: A cross-sectional Spanish nationwide study of 405 cases.Br J Dermatol. 2021; Crossref PubMed Scopus (93) Google Scholar; Johansen et al., 2021Johansen M Chisolm SS Aspey LD Brahmbhatt M. Pityriasis rosea in otherwise asymptomatic confirmed COVID-19-positive patients: A report of 2 cases.JAAD Case Rep. 2021; 7: 93-94Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar; Marcantonio-Santa Cruz et al., 2021Marcantonio-Santa Cruz OY Vidal-Navarro A Pesque D Gimenez-Arnau AM Pujol RM Martin-Ezquerra G Pityriasis rosea developing after COVID-19 vaccination.J Eur Acad Dermatol Venereol. 2021; Crossref PubMed Scopus (13) Google Scholar; McMahon et al., 2021McMahon DE Amerson E Rosenbach M Lipoff JB Moustafa D Tyagi A et al.Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.J Am Acad Dermatol. 2021; 85: 46-55Abstract Full Text Full Text PDF PubMed Scopus (436) Google Scholar). It is easy to overlook because the incidence of PR as a side effect of COVID-19 vaccination is extremely low, accounting for about 0.96% of all cutaneous reactions (McMahon et al., 2021McMahon DE Amerson E Rosenbach M Lipoff JB Moustafa D Tyagi A et al.Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.J Am Acad Dermatol. 2021; 85: 46-55Abstract Full Text Full Text PDF PubMed Scopus (436) Google Scholar). A 29-year-old man presented with a herald patch on his right chest 2 hours after the second dose of mRNA-1273 COVID-19 vaccination (Figure 1A). Within 2–3 days, multiple skin lesions rapidly disseminated to the upper trunk and extremities (Figure 1B). He had no other systemic symptoms and no previous history of COVID-19 infection. Skin biopsy showed focal parakeratosis, spongiosis, and superficial perivascular inflammatory infiltrates (Figure 1C). Based on the clinical and histological features he was diagnosed with PR.Figure 1(A) A 3 × 4 cm sized, solitary large, erythematous patch with trailing scale (herald patch, white arrow) on his right chest. (B) Multiple oval, salmon-colored patches along the lines of cleavage on the trunk. (C) Histopathologic examination shows patchy parakeratosis, mild spongiosis, and perivascular lymphocytic infiltration. (Hematoxylin and Eosin, original magnification × 100).View Large Image Figure ViewerDownload Hi-res image Download (PPT) According to Ogata et al. (Ogata et al., 2021Ogata AF Cheng CA Desjardins M Senussi Y Sherman AC Powell M et al.Circulating SARS-CoV-2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients.Clin Infect Dis. 2021; Crossref PubMed Scopus (55) Google Scholar), the SARS-CoV-2 viral spike protein antigen is detected as early as day 1 post-vaccination, and peak levels are detected after an average of 5 days. Based on the literature, the time lapse between COVID-19 vaccination and skin lesions ranges 5–17 days, with an average of 12.7 days. However, our patient developed PR after only 2 hours of receiving the vaccination, which is a very short time interval. This case did not enable a conclusion to be made that a true causal link exists between PR and vaccination. This is because the short interval of 2 hours may be insufficient for the vaccine to circulate throughout the bloodstream and induce an appropriate immune response. However, in this patient, the skin lesions occurred after the second dose of the vaccination, and it is possible that PR may occur sooner in such cases than after the first dose of the vaccination. Johnston et al. (Johnston et al., 2021Johnston MS Galan A Watsky KL Little AJ. Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series.JAMA Dermatol. 2021; 157: 716-720Crossref PubMed Scopus (84) Google Scholar) recently reported that delayed localized cutaneous reactions may occur sooner after the second administration of the vaccine. Moreover, a previous history of PR is not generally related to recurrence or onset of the lesion, and is not an important consideration for this patient because there was no history of PR. Therefore, in the future, researchers should study the onset duration of cutaneous reactions that occur following the administration of the first and second doses of the COVID-19 vaccine. None. This study was performed in accordance with the Helsinki Declaration and the patient provided written informed consent for the publication of his case details. None. The authors have no conflicts of interest to declare.

Paracoccidioidomycosis in an Elderly Simulating Cholangiocarcinoma

Paracoccidioidomycosis, the most prevalent deep mycosis in Latin America, is caused by dimorphic species of the genus Paracoccidioides, affects predominantly male rural workers between 30-50 years of age and is an important cause of morbidity and mortality. It can present in two clinical forms: acute/subacute or chronic. In rare cases paracoccidioidomycosis may simulate neoplasia and must be considered as a differential diagnosis of intra-abdominal tumors in endemic areas. We report an exuberant case of subacute paracoccidioidomycosis in an elderly lady, although it is more frequent in the juvenile form. Multiple facial skin lesions were associated with a wasting syndrome and extensive adenopathy including in the hepatic area, causing bile duct dilatation simulating a cholangiocarcinoma. Skin histopathology was diagnostic and antifungal treatment allowed complete resolution of cutaneous and systemic lesions, thus highlighting the merit of the dermatologist, who was fundamental for the conclusive diagnosis and institution of specific therapy, resulting in a favorable outcome.

Associations between multiple sclerosis and skin lesion: About five cases

Vitiligo, Psoriasis and alopecia areata, a common chronic inflammatory disease, increases the risk of developing multiple sclerosis (MS), but evidence for this outcome is still unclear. This relation does not appear to be more common in patients with MS or their relatives. It may also be a rare side effect of treatment Related complication of MS.

A Rare Skin Disorder with Bacteremia in a Neonate.

A Rare Skin Disorder with Bacteremia in a Neonate.

296 The Reverse of Medal – Dermatological Complications After Renal Transplantation

Kidney transplant represent the last resort for the patients with end-stage renal disease, but this revolutionary method of treatment is accompanied by multiple complications, the dermatological being among the most common. Bassal cell carcinoma, squamous cell carcinoma, cutaneous lymphoma and Kaposi’s sarcoma are just few of the complications. We present the case of a 62 years old patient, which at the age of 54 he underwent a kidney transplant, without other personal pathological history. This patient presented to the clinic for multiple skin lesions: on the right earlobe and nasal wing, on the right arm and on the bilateral legs, with slow evolution of about two years, round-ovals, relatively well delimited, with dimensions between 0.4/0.3cm-2.5/2.4cm, red-brown, covered by bloody crusts (lesions located in the calves).

Intelligent Dermatologist Tool for Classifying Multiple Skin Cancer Subtypes by Incorporating Manifold Radiomics Features Categories.

The rates of skin cancer (SC) are rising every year and becoming a critical health issue worldwide. SC's early and accurate diagnosis is the key procedure to reduce these rates and improve survivability. However, the manual diagnosis is exhausting, complicated, expensive, prone to diagnostic error, and highly dependent on the dermatologist's experience and abilities. Thus, there is a vital need to create automated dermatologist tools that are capable of accurately classifying SC subclasses. Recently, artificial intelligence (AI) techniques including machine learning (ML) and deep learning (DL) have verified the success of computer-assisted dermatologist tools in the automatic diagnosis and detection of SC diseases. Previous AI-based dermatologist tools are based on features which are either high-level features based on DL methods or low-level features based on handcrafted operations. Most of them were constructed for binary classification of SC. This study proposes an intelligent dermatologist tool to accurately diagnose multiple skin lesions automatically. This tool incorporates manifold radiomics features categories involving high-level features such as ResNet-50, DenseNet-201, and DarkNet-53 and low-level features including discrete wavelet transform (DWT) and local binary pattern (LBP). The results of the proposed intelligent tool prove that merging manifold features of different categories has a high influence on the classification accuracy. Moreover, these results are superior to those obtained by other related AI-based dermatologist tools. Therefore, the proposed intelligent tool can be used by dermatologists to help them in the accurate diagnosis of the SC subcategory. It can also overcome manual diagnosis limitations, reduce the rates of infection, and enhance survival rates.

Treatment of Relapsing HPV Diseases by Restored Function of Natural Killer Cells

SummaryHuman papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions. (Funded by the National Institutes of Health and the Herbert Irving Comprehensive Cancer Center Flow Cytometry Shared Resources.)

What to Look Out for in a Newborn with Multiple Papulonodular Skin Lesions at Birth.

Multiple papulonodular skin lesions at birth can indicate the presence of various benign and malignant disorders. Although the lesions’ clinical aspect (color and consistency, in particular) may steer the clinician towards one disorder or another (infantile myofibromatosis, xanthogranuloma, or metastatic neuroblastoma), the diagnosis can only be confirmed by the histopathologic assessment of a biopsy. In neonates, a rapid but accurate diagnosis is critical because skin lesions may be the first manifestation of a malignant disorder like leukemia cutis or metastatic neuroblastoma. Here, we review the various disorders that may manifest themselves as multiple skin lesions at birth.

Cutaneous pilar leiomyoma completely treatable by surgical resection, a case report.

Background: Cutaneous pillar leiomyoma (CPL) is a benign skin tumour of errector pili muscles and is rare condition. Clinically it appears as small nodule which are in the form of small groups. These are tender to touch, pressure, cold, and emotional stimuli. Different modalities have been tried to reduce pain and discomfort. Surgery is a treatment of choice in lesion which are very tender and associated with disturbance of social life. The objective of treatment in to achieve complete cure from pain with functional and aesthetic improvement. Case: A case of a male patient age 28 years, with multiple cutaneous leiomyomas on the left anterior chest wall and lateral chest wall. On clinical examination there were multiple nodular skin lesions that manifested as brownish erythematous. The lesions increased gradually during the last 2 years, extending to the left lateral chest wall. Complete surgical excision of tumor was done, followed by coverage with split thickness skin graft taken from the thigh. Patient was followed up fortnightly up to six month. Results: After surgical treatment, there was complete pain relief and acceptable cosmetic outcome, which allowed the social reintegration. Conclusion: Cutaneous pilus leiomyomas is difficult to treat. The radical resection of tumor is important to resolve the symptoms with prevention of tumor recurrence.

Factitious Cushing's syndrome, hypopituitarism, and self-provoked skin lesions: when the skin mirrors the soul.

SummaryFactitious Cushing’s syndrome (CS) is a very rare form of Münchausen syndrome. Its presentation and course are extremely heterogeneous, and diagnosis is generally challenging. We report the case of a 52-year-old woman who was initially investigated because of the occurrence of cushingoid features. Nevertheless, endocrine work-up showed very low morning plasma ACTH and serum cortisol levels. In addition, it also demonstrated central hypopituitarism and hypogonadotropic hypogonadism. Head MRI showed a small pituitary mass. Based on these results, and probably overlooking the initial clinical suspicion, general practitioner (GP) referred the patient to our Endocrine Unit for hypopituitarism. At inspection, moon face, central obesity, and bruising were evident. Multiple ulcerative skin lesions were also concentrated in the right arm and leg. Dermatology evaluation suggested that the lesions were self-provoked. For several days, the patient denied the assumption of corticosteroids, but we finally discovered that the GP’ nurse had prescribed betamethasone without the GP’s knowledge for about 2 years. In conclusion, the surreptitious assumption of corticosteroids is very rare, but the physicians should be aware that pituitary function could be impaired by high doses of corticosteroids, mimicking hypopituitarism. In these patients, a multidisciplinary approach and environmental investigation can be useful to diagnose factitious CS.Learning pointsSurreptitious assumption of corticosteroids can cause heterogeneous presentation, ranging from Cushing’s syndrome to multiple hypopituitarism.Suppression of ACTH and cortisol levels in a patient with cushingoid features firstly suggests surreptitious assumption of corticosteroids.A multidisciplinary approach can be extremely useful in patients with suspected factitious Cushing’s syndrome.Sometimes, to prove surreptitious assumption of corticosteroids needs environmental investigation.

A case of disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum with CARD9 mutation.

Phaeohypomycosis is a rare cutaneous and subcutaneous fungal infection caused by dematiaceous fungi. They have a widespread global distribution occasionally affecting humans. A 26-year-old woman presented with multiple skin lesions over her face and extremities for last 7 years, unresponsive to systemic amphotericin B and itraconazole. Further investigations revealed CARD9 mutation and phaeohyphomycosis caused by the pigmented fungus Exserohilum rosatratum. Lesions subsequently improved with oral flucytosine and itraconazole.

NODULAR SCLEROSIS HOGDKINS LYMPHOMA GRADE 2 MIMICKING ANAPLASTIC LARGE CELL LYMPHOMA - A CASE REPORT

INTRODUCTION: Hodgkin's lymphoma (HL) is a lymphoproliferative neoplasm constituting less than 1% of all neoplasms. It has been categorized into- nodular lymphocyte predominant HL and classical type with subtypeslymphocyte rich, lymphocyte depleted, nodular sclerosis and mixed cellularity. Nodular sclerosis Hodgkin's lymphoma (NSHL) is difcult to diagnose on FNA because of the lack of Reed Sternberg (RS) cells, low cellularity and difculty in identifying the counterpart of lacunar cells. CASE A 16-year-old female presented with anterior chest wall swelling si REPORT: nce 6 months measuring 5x4cm along with incidentally noted cervical lymph nodes measuring 2x2cm and 1x1cm. On examination, multiple papular skin lesions were observed. FNAC smears from cervical lymph node showed high cellularity, with sheets of binucleated and multinucleated cells having multiple nucleoli, some showing pale bluish abundant cytoplasm whereas others showing dense cytoplasm; in a background of reactive lymphoid population with few neutrophils. Few giant cells showed hyperchromatic nuclei. Abnormal mitosis seen. No typical RS cell was seen. Peripheral blood smear showed neutrophilic leukocytosis with no atypical cell. Possibility of NSHL was considered and biopsy advised to rule out ALCL. Histological sections showed near total effacement of lymph node architecture by nodules separated by broad brotic bands. These nodules exhibit proliferating lymphocytes with clustered lacunar cells along with some mononucleate, binucleate and multinucleated cells. Prominent mitotic activity, angiogenesis, focal micro abscesses were noted. Immunohistochemistry showed CD 15+ and CD 30+ expression in the giant cells, conrming diagnosis of NSHL grade 2. NSHL poses a cytological diagnostic dilemma specially in abse CONCLUSION: nce of sclerosis on FNA, making histological examination and IHC mandatory

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

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, 2008 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.