Atypical Clinical Presentation Research Articles

Implications of anti-ganglioside antibodies in isolated dysphagia following COVID-19 infection: Case series.

There have been multiple reports about the occurrence of dysphagia after the contraction of coronavirus disease 2019 (COVID-19). However, a detailed pathology and epidemiologic relation between COVID-19 infection and dysphagia have yet to be established. Here, we report three cases of unexplained dysphagia after COVID-19 diagnosis, with atypical clinical presentations. All patients showed severe isolated lower cranial nerve involvement with dysphagia and aspiration, which required full tube feeding but showed no evidence of limb weakness or sensory symptoms. All tested positive for anti-ganglioside antibody tests, which all commonly (GD1b, GM1, and GQ1b) are known to have terminal NeuNAc(α2-3)Gal epitope. We report a series of cases featuring severe, isolated dysphagia post-COVID-19 infection, concomitant with positive anti-ganglioside antibodies. One potential etiology is a variant of Guillain-Barré syndrome. Because only isolated dysphagia with sparing of the facial and extraocular muscles was evident in these cases, we explore the association between anti-ganglioside antibodies specific to NeuNAc(α2-3)Gal, which has been frequently associated with the development of bulbar dysfunction. Given that NeuNAc(α2-3)Gal exhibits an affinity for the spike glycoprotein of SARS-CoV-2, a cross-reaction against NeuNAc(α2-3)Gal may possibly contribute to isolated dysphagia following COVID-19 infection.

CD4/CD8 double-negative mycosis fungoides: a review

Mycosis Fungoides (MF) stands as the predominant form of primary cutaneous T-cell lymphoma (CTCL). It manifests a diverse array of clinical, histological, and immunophenotypic variations, each bearing distinct prognostic implications. The typical immunophenotypic profile of mycosis fungoides involves CD3+/CD4+/CD45RO+ memory T cells. Notably, the CD4-/CD8- double-negative variant of MF is a rare occurrence, observed in approximately 12% of early-stage cases and more prevalent in tumor-stage instances, often correlated with atypical clinical presentations. Despite its rarity, scant information is available about double-negative Mycosis Fungoides, with only a limited number of cases documented in the existing literature. This review aims to provide enhanced clarity, comprehension, and a detailed exploration of the spectrum encompassing double-negative mycosis fungoides.

Systemic and Bilateral Severe Ocular Toxoplasmosis Resembling Autoimmune Phenomena: A Case Report.

To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment. A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient's condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage. This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.

Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of 131I-Whole-Body Scintigraphy with Regional SPECT/CT

Unusual Metastatic Sites and Radioiodine Uptake in Patients of Differentiated Thyroid Carcinoma with Atypical Clinical Presentations: Utilization of 131I-Whole-Body Scintigraphy with Regional SPECT/CT

Darier disease: Histopathology revisited.

Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.

Cutaneous Tuberculosis: A Case Report of an Atypical Clinical and Dermoscopical Presentation

Tuberculosis is an endemic disease in Morocco caused by the Mycobacterium tuberculosis. Cutaneous forms are rare, they account for 1-2% of extra-pulmonary localizations of tuberculosis. The diagnosis of cutaneous TB often poses a challenge to clinicians because of its clinical polymorphism and it is based by histology, QuantiFERON-TB Gold test, and polymerase chain reaction. Treatment consists of a combination of antibiotics. Herein we report a case report of an atypical clinical and dermoscopical presentation of cutaneous tuberculosis.

Vancomycin-Resistant Streptococcus thoraltensis: A Case Report of Bacterial Endocarditis and Review of Literature on Infections Caused by This Pathogen.

Streptococcus thoraltensis is a rare species, part of the viridans streptococcus group, found initially in rabbits and pigs, which can be vancomycin-resistant. We present the case of a 65-year-old patient, a smoker and chronic alcohol consumer with chronic obstructive pulmonary disease (COPD) and multiple dental foci who had been diagnosed with bacterial endocarditis caused by Streptococcus thoraltensis. The particular elements of the case consisted of an atypical clinical presentation with diarrheal stools, abdominal pain, concomitant damage to the aortic and tricuspid valves, the presence of large vegetations (>2 cm), and a vancomycin-resistant strain of Streptococcus thoraltensis. The evolution of the patient was unfavorable due to septic embolisms, respiratory failure requiring orotracheal intubation, and septic and cardiogenic shock. Infections with Streptococcus thoraltensis are challenging to treat because of the severity of the clinical form it causes and the pattern of antibiotic resistance in this germ. Based on our brief review, Streptococcus thoraltensis is an extremely rare human pathogen previously described as the etiologic agent of infectious endocarditis in only one case.

A career in solving clinical-pathological conundrums: Heyde syndrome, anti-platelet factor 4 disorders, and microvascular limb ischemic necrosis.

Hematology is a clinical specialty with strong roots in the laboratory; accordingly, the lab can help solve perplexing clinical problems. This review highlights clinical-pathological conundrums addressed during my 35-year hematology career at McMaster University. Heyde syndrome is the association between aortic stenosis and bleeding gastrointestinal (GI) angiodysplasia where the bleeding is usually cured by aortic valve replacement; the chance reading of a neonatal study showing reversible deficiency of high-molecular-weight (HMW) multimers of von Willebrand factor (vWF) following surgical correction of congenital heart disease provided the key insight that a subtle deficiency of HMW multimers of vWF explains Heyde syndrome. The unusual immunobiology of heparin-induced thrombocytopenia (HIT)-a highly prothrombotic, antibody-mediated, anti-platelet factor 4 (PF4) disorder featuring rapid appearance and then disappearance (seroreversion) of the pathological heparin-dependent platelet-activating antibodies-permitted identification of key clinical features that informed development of a scoring system (4Ts) to aid in HIT diagnosis. Atypical clinical presentations of HIT prompted identification of heparin-independent anti-PF4 antibodies, now recognized as the explanation for vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as VITT-like disorders triggered by adenovirus infection. Another unusual feature of HIT is its strong association with limb ischemia, including limb necrosis secondary to deep-vein/microvascular thrombosis (venous limb gangrene). The remarkable observation that supratherapeutic warfarin anticoagulation predisposes to HIT- and cancer-associated venous limb gangrene provided insight into disturbed procoagulant/anticoagulant balance; these concepts are relevant to microvascular thrombosis in critical illness (symmetrical peripheral gangrene), including a pathophysiological role for proximate "shock liver" (impaired hepatic synthesis of natural anticoagulants).

A Cross-Sectional Study of Epidemiological and Clinical Aspects of Pityriasis Rosea along with Dermoscopic Analysis and Histopathology Correlation

Background: Pityriasis Rosea (PR) is a common, yet enigmatic, dermatological condition characterized by a distinctive clinical presentation. Despite its prevalence, the aetiology and pathogenesis of PR remain elusive. Aims: To study the epidemiological and clinical aspects of patients with PR. To study dermoscopic findings and carry out histopathological correlation. Methods: A cross-sectional study of 50 patients was conducted. A detailed clinical history was taken and an examination was done followed by a dermoscopy. Quantitative data like age and duration of disease are presented with the help of standard deviation. Qualitative risk factors, like gender, age groups, symptomatology, site of lesion, findings or cutaneous examination, dermoscopy findings, and histopathology findings, are presented with the help of frequency and percentages. Results: PR shows male preponderance and mean age of occurrence being 30.8 ± 15.7 years. Forty per cent of patients had an atypical clinical presentation. The most frequently seen dermoscopy findings were diffuse red background (58%), peripheral collarette scale (62%), and peripheral dotted vessels (50%). On histopathology, the most common findings were spongiosis (44%), parakeratosis (38%), irregular acanthosis (34%), perivascular lymphocytic infiltrate (56%), and red blood cell extravasation (36%). Limitations: Sample size was less due to COVID. As this was a corss-sectional study follow up of patients could not be done. Conclusion: While the diagnosis of PR is clinical, it is difficult in atypical cases where dermoscopy comes to the aid. It also helps identify the age of lesions, thus helping decide the treatment strategy for patients. Biopsy remains the gold standard in ruling out other differentials of PR.

Sudden hearing loss secondary to syphilis

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum, whose incidence has increased significantly in recent years. Some patients may develop sudden hearing loss (SHL) against the background of otosyphilis. The objective of our study was to determine whether routine lues serology is useful in patients presenting with sudden hearing loss. For this purpose, all cases of SHL treated in our hospital during a period of 6years were propectively collected. The frequency of positivity for syphilis in these patients, the treatment received, and their evolution were determined. Of the total number of patients evaluated during that period, 71 underwent serological screening for syphilis, of whom 2 (2.8%) presented positive screening antibodies. In one of them, the RPR was normal and had been treated with lues a few years before. After treatment there was no improvement. The other patient, diagnosed with otosyphilis with unconfirmed suspected neurological disease, showed normalization of hearing after specific treatment. Since it is a potentially curable disease, despite the low overall frequency of syphilis in patients with SHL it is advisable to perform serological screening for syphilis in high risk patients (e.g., incarceration, multiple recent sexual partners, men who have sex with men) or atypical clinical presentation (e.g., concurrent neuropathies).

Paroxysmal Dystonic Posturing Mimicking Nocturnal Leg Cramps as a Presenting Sign in an Infant with DCC Mutation, Callosal Agenesis and Mirror Movements.

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient's clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband's father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations.

A rapidly growing nodule on the face during pregnancy.

It is well known that adnexal skin tumors can simulate other cutaneous neoplasia and that various types of benign and malignant skin tumors can develop or modify during pregnancy. Here, we report a case of trichoblastoma mimicking a keratoacanthoma arising in a nevus sebaceous during pregnancy. Given its unique clinical and dermoscopic features, this case highlights the pivotal role of clinicopathological correlation in the diagnosis of adnexal tumors with an atypical clinical presentation.

Morgellons disease: a narrative review.

Morgellons disease is characterized by the persistent delusion of skin infestation, ultimately inflicting wounds and impairing quality of life. There is insufficient and conflicting research pertaining to this condition, imposing challenges on clinicians in understanding, diagnosing, and treating it. In this review, we summarize the available literature on Morgellons disease including its historical evolution, epidemiology, proposed pathophysiology, underlying structural and functional brain pathologies, typical and atypical clinical presentations, diagnosis, and treatment. A comprehensive review of the literature was conducted on PubMed, Embase, and Scopus using specified keywords. Selected articles were screened by two independent reviewers based on set inclusion and exclusion criteria. Conflicts were resolved by a third reviewer as needed. No limit to the date of selected articles was set due to the scarce literature available on the subject. Morgellons disease is an underdiagnosed entity, owing mostly to the lack of an established pathophysiology and treatment guidelines. While many authors classify it as a type of delusional infestation (DI), others correlate MD with an underlying spirochetal infection, namely Lyme disease. Neuroimaging studies have revealed abnormalities in the "fronto-striato-thalamo-parietal network", a finding common to patients with DI, in addition to alterations in structures related to the "Itch Processing Pathway". Patients tend to extract fibers from their skin lesions and place them in a match box hence the term "match box sign". The diagnosis is that of exclusion, requiring extensive work up to rule out secondary causes and differential diagnoses. Treatment is largely based on the use of antipsychotics, with or without cognitive behavioral therapy. Despite being a diagnosis of exclusion, clinicians must be aware of this entity and have a profound understanding of the pathogenesis underlying it. Upon clinical suspicion, secondary Morgellons should always be ruled out through a thorough history taking, physical examination, and laboratory exams. Despite the challenges brought by the heterogeneous presentation of the condition and the paucity of research revolving around it, the great impact that Morgellons disease has on patients' quality of life forms a pressing need for its adequate detection, diagnosis, and treatment.

Miliary Tuberculosis as Postmortem Diagnosis in Solid Organ Transplant Recipient: Case Report and Review of the Literature

The diagnosis of tuberculosis (TB) in solid organ transplant (SOT) recipients presents challenges that may lead to treatment delay. These include atypical clinical presentations, increased likelihood of negative tuberculin skin test or/and interferon-gamma release assays, and negative sputum smear results despite active disease. The treatment poses challenges due to pharmacokinetic interactions, allograft-related toxicity, and inadequate immune response. We report the case of a 70-year-old man after kidney transplantation in 2012. The patient was transferred from the urology unit with deteriorating renal function and presumed urosepsis. His pulmonary chest X-ray showed hilar pulmonary infiltrates. Computed tomography of the chest/abdomen/pelvis revealed mediastinal lymphadenopathy, pulmonary infiltrates, pulmonary effusion, and splenomegaly. His blood results showed pancytopenia and high inflammatory and renal markers. He was treated with broad-spectrum antibiotics covering bacterial, fungal, and viral infections. Despite initial clinical improvement, his kidney function deteriorated, and he required hemodialysis. His temperature continued to spike. On physical examination, he was confused and lethargic. He was scheduled to have a mediastinoscopy with lymph node biopsy, but he died the day before. The postmortem examination revealed miliary tuberculosis with tuberculosis of many organs: kidney transplant, native kidney, bone marrow, mediastinal lymph nodes, lungs, and spleen. The diagnosis of active TB in transplant recipients requires a high index of suspicion and invasive procedures. The majority of all cases of active TB after SOT are disseminated or occur at extrapulmonary sites. Only a small minority of patients have classic cavitary changes on pulmonary imaging.

A new blood DNA methylation signature for Koolen-de Vries syndrome: Classification of missense KANSL1 variants and comparison to fibroblast cells

Pathogenic variants in KANSL1 and 17q21.31 microdeletions are causative of Koolen-de Vries syndrome (KdVS), a neurodevelopmental syndrome with characteristic facial dysmorphia. Our previous work has shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes have identifiable patterns of DNA methylation (DNAm) change: DNAm signatures or episignatures. Given the role of KANSL1 in histone acetylation, we tested whether variants underlying KdVS are associated with a DNAm signature. We profiled whole-blood DNAm for 13 individuals with KANSL1 variants, four individuals with 17q21.31 microdeletions, and 21 typically developing individuals, using Illumina’s Infinium EPIC array. In this study, we identified a robust DNAm signature of 456 significant CpG sites in 8 individuals with KdVS, a pattern independently validated in an additional 7 individuals with KdVS. We also demonstrate the diagnostic utility of the signature and classify two KANSL1 VUS as well as four variants in individuals with atypical clinical presentation. Lastly, we investigated tissue-specific DNAm changes in fibroblast cells from individuals with KdVS. Collectively, our findings contribute to the understanding of the epigenetic landscape related to KdVS and aid in the diagnosis and classification of variants in this structurally complex genomic region.

Herpes Zoster in Palate: Atypical Presentation in Immunosuppressed Patient Secondary to Rituximab, a Case Report and Review of Clinical Manifestations and Management

Herpes zoster (HZ) is caused by the reactivation of the latent varicella zoster virus (vZv). The cause of reactivation may be associated with predisposing factors such as age, stress or the impaired immune system and an association with autoimmune diseases has been seen. Its clinical presentation is characterized by the appearance of multiple vesicles that rupture quickly, leaving small, very painful ulcers that are distributed respecting specific dermatomes. The diagnosis in most cases is clinical, and complementary tests may be necessary and differential diagnoses may be excluded in cases of atypical presentation. The main sequelae after the disappearance of skin signs is postherpetic neuralgia, which is more common in the elderly. Early diagnosis and rapid initiation of treatment determine the prognosis, especially in immunocompromised individuals. In this work we report a case of atypical clinical presentation in a woman with autoimmune disease, immunocompromised and belonging to the elderly population, being a clear example of the patient in whom special attention should be paid when establishing the diagnosis with the aim of emphasizing early detection and rapid establishment of appropriate treatment, avoiding deleterious outcomes.

Cutaneous Hyalohyphomycosis and Its Atypical Clinical Presentations in Immunosuppressed Patients.

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera.

Do patients with diabetes with new onset acute myocardial infarction present with different symptoms than non-diabetic patients?

The objective of this study was to investigate the differences in presenting symptoms between patients with and without diabetes being diagnosed with an acute myocardial infarction (AMI). A total of 5,900 patients with a first-time AMI were included into the analysis. All patients aged between 25 and 84 years were recorded by the population-based Myocardial Infarction Registry in Augsburg, Germany, between 2010 and 2017. The presence (yes/no) of 12 AMI typical symptoms during the acute event was assessed within the scope of a face-to-face interview. Multivariable adjusted logistic regression models were calculated to analyze the associations between presenting symptoms and diabetes mellitus in AMI patients. Patients with diabetes had significantly less frequent typical pain symptoms, including typical chest pain. Also, other symptoms like sweating, vomiting/nausea, dizziness/vertigo and fear of death/feeling of annihilation occurred significantly more likely in non-diabetic patients. The only exception was the symptom of shortness of breath, which was found significantly more often in patients with diabetes. In multivariable-adjusted regression models, however, the observed effects were attenuated. In patients younger than 55 years, the associations between diabetes and various symptoms were mainly missing. Type 2 diabetes mellitus is a risk factor not only for the development of AMI, but is also associated with an adverse outcome after AMI. Atypical clinical presentation additionally complicates the diagnostic process. It is therefore essential for physicians to be aware of the more often atypical symptoms that diabetic AMI patients report.

A curious case of expanded dengue syndrome.

Dengue fever (DF) primarily presents with fever, headache, malaise, bleeding manifestations and haemoconcentration. World Health Organization (WHO) classifies DF according to levels of severity: (a) without warning signs; (b) with warning signs, such as abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing haematocrit and thrombocytopenia; and (c) severe dengue with severe plasma leakage, severe bleeding or organ failure. Atypical clinical presentations of DF are defined as expanded dengue syndrome: this includes renal, cardiac, hepatic or cerebral damage. We report such a severe case where a young man developed acute kidney injury, acute fulminant liver failure and acute pancreatitis secondary to DF, but recovered.

“Miliary lung parenchymal opacities” as presenting feature of metastatic papillary type of thyroid malignancy: It’s not tuberculosis always!

Pulmonary tuberculosis (TB) is the most common cause of mortality and morbidity in South East Asia due to infective causes and tops the list of all infectious etiologies in India. Radiological presentations in pulmonary TB are diverse with the most common in them, which are nodules, consolidation, cavitation, and lung parenchymal destruction with or without collapse and consolidation. In this case report, a 31-year-old female presented with constitutional symptoms with miliary opacities in chest X-ray without microbiological evidence for TB in smear microscopy or nucleic acid amplification tests. She was treated as a case of miliary TB with antituberculosis treatment (ATT) on two occasions in the past 2 years as an “X-ray-positive case” on the basis of symptoms and chest radiology findings. She was never shown any clinical and radiological response in the past 1½ years in spite of satisfactory ATT adherence and compliance. After retrospective analysis of this case at our center, we have documented worsening of radiological findings and chest high-resolution computed tomography conformed miliary nodules and not typical miliary mottling favoring TB. We have noted right thyroid enlargement with a nodule in contrast tomography of neck. Fine-needle aspiration cytology confirmed as papillary carcinoma of the thyroid. We have confirmed this case as miliary metastasis due to primary thyroid malignancy. Miliary metastasis should be considered in cases with atypical radiological and clinical presentations with negative microbiological workup. No empirical ATT should be offered in the era of highly sensitive nucleic acid amplification tests and the term “X-ray-positive with negative microbiological tests” should be phased out.