Atypical Presentation of a Rare Disease: Eosinophilic Cholangitis Posing as a Cancer.

Am J Case Rep. 2018 Jan 22;19:76-81

Authors: Hoilat JN, Hoilat GJ, AlQahtani S, Alhussaini HF, Alabbad SI

Abstract
BACKGROUND A variety of benign etiologies of biliary stricture may initially be mistaken for hilar cholangiocarcinoma. Consequently, many patients undergo surgery for a benign disease that could have been treated medically. Eosinophilic cholangitis (EC) is an uncommon, benign, self-limiting disease that should be considered when approaching a case of obstructive jaundice since it causes biliary stricture formation. Transmural eosinophilic infiltration of the biliary tree is characteristic of EC. It may initially be indistinguishable from hilar cholangiocarcinoma. CASE REPORT We present a rare case of an 84-year-old male who was referred to our hospital for abdominal mass investigation with the provisional diagnosis of cholangiocarcinoma. During the workup, the index of suspicion for malignancy remained high as the typical laboratory and radiological findings for benign causes of biliary stricture were not present. Hence, the patient underwent left hepatectomy with caudate lobe resection and received a retrograde diagnosis of EC. CONCLUSIONS This case demonstrates that EC could present in the elderly with cardinal signs of cancer and absence of the typical findings of EC which was not previously reported. Since only 70% of patients present with peripheral eosinophilia, we stress on the importance of implementing diagnostic criteria for EC in the setting where peripheral eosinophilia is absent. Furthermore, this disorder has been reported to respond well to steroid therapy, hence, diagnostic criteria for EC would provide another treatment option for elderly and/or those who are not fit for surgery.

PMID: 29353872 [PubMed - indexed for MEDLINE]

Usage of Molecular Pathology in a Rare Oral Tuberculosis Diagnosis.

Chin Med J (Engl). 2017 Mar 05;130(5):627-628

Authors: Nie WJ, Che NY, Cai BY, Chu NH

PMID: 28230001 [PubMed - indexed for MEDLINE]

Rare sinonasal lesions.

Rom J Morphol Embryol. 2017;58(4):1541-1547

Authors: Sarău CA, Poenaru M, Balica NC, Baderca F

Abstract
Rare naso-sinonasal lesions represent a diagnostic challenge for clinicians because of the paucity of the cases and similarities with other more frequently sinonasal pathologies. The aim of the study was to present five rare sinonasal lesions in order to emphasize their symptomatology, imaging aspects, histopathological features, algorithms of diagnosis, and strategies of treatment and importance of teamwork between clinicians, pathologists and radiologists for a correct and prompt diagnosis.
CASE PRESENTATIONS: The cases were represented by patients with nasal sarcoidosis, nasal primitive neuroectodermal tumors, sinonasal mucosal melanoma, sinonasal plasmacytomas and nasal-type extranodal natural killer (NK) T-cell lymphoma. All the patients were biopsied in the Department of ENT (Ear, Nose and Throat), "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania, and the diagnosis was made using routine and immunohistochemical (IHC) stainings. The patients with sinonasal melanoma and the patient with extranodal NK T-cell lymphoma died in few months after diagnosis, despite treatment. Rare sinonasal lesions share similar symptomatology and imaging aspects with other, more frequently diagnosed entities. The cases reported in this paper showed the same pattern as those presented in other studies; the symptomatology, diagnosis, treatment and prognosis were the same. Clinical examination, imaging studies and routine and IHC markers guides us to the right diagnosis that should be prompt because of the prognosis of some tumors. The treatment has a few characteristics: surgery excision within safe margins, working with other specialties (oncology, radiotherapy, hematology, nephrology, pneumology), follow-up and correctly informing the patient being mandatory.
CONCLUSIONS: In this paper, there were presented five interesting cases of rare sinonasal lesions, in order to highlight the importance of teamwork for a quick and correct diagnosis.

PMID: 29556655 [PubMed - indexed for MEDLINE]

Integrated genetic and pharmacologic interrogation of rare cancers.

Nat Commun. 2016 06 22;7:11987

Authors: Hong AL, Tseng YY, Cowley GS, Jonas O, Cheah JH, Kynnap BD, Doshi MB, Oh C, Meyer SC, Church AJ, Gill S, Bielski CM, Keskula P, Imamovic A, Howell S, Kryukov GV, Clemons PA, Tsherniak A, Vazquez F, Crompton BD, Shamji AF, Rodriguez-Galindo C, Janeway KA, Roberts CW, Stegmaier K, van Hummelen P, Cima MJ, Langer RS, Garraway LA, Schreiber SL, Root DE, Hahn WC, Boehm JS

Abstract
Identifying therapeutic targets in rare cancers remains challenging due to the paucity of established models to perform preclinical studies. As a proof-of-concept, we developed a patient-derived cancer cell line, CLF-PED-015-T, from a paediatric patient with a rare undifferentiated sarcoma. Here, we confirm that this cell line recapitulates the histology and harbours the majority of the somatic genetic alterations found in a metastatic lesion isolated at first relapse. We then perform pooled CRISPR-Cas9 and RNAi loss-of-function screens and a small-molecule screen focused on druggable cancer targets. Integrating these three complementary and orthogonal methods, we identify CDK4 and XPO1 as potential therapeutic targets in this cancer, which has no known alterations in these genes. These observations establish an approach that integrates new patient-derived models, functional genomics and chemical screens to facilitate the discovery of targets in rare cancers.

PMID: 27329820 [PubMed - indexed for MEDLINE]

The Nrf2-Antioxidant Response Element Signaling Pathway Controls Fibrosis and Autoimmunity in Scleroderma.

Front Immunol. 2018;9:1896

Authors: Kavian N, Mehlal S, Jeljeli M, Saidu NEB, Nicco C, Cerles O, Chouzenoux S, Cauvet A, Camus C, Ait-Djoudi M, Chéreau C, Kerdine-Römer S, Allanore Y, Batteux F

Abstract
Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and internal organs and vascular alterations. Dysregulations in the oxidant/antioxidant balance are known to be a major factor in the pathogenesis of the disease. Indeed, reactive oxygen species (ROS) trigger neoepitopes leading to a breach of immune tolerance and autoimmune responses, activate fibroblasts to proliferate and to produce excess of type I collagen. ROS also alter endothelial cells leading to vascular dysfunction. Glutathione (GSH) is the most potent antioxidant system in eukaryotic cells. Numerous studies have reported a defect in GSH in SSc animal models and humans, but the origin of this defect remains unknown. The transcription factor NRF2 is a key player in the antioxidant defense, as it can induce the transcription of antioxidant and cytoprotective genes, including GSH, through its interaction with the antioxidant response elements. In this work, we investigated whether NRF2 could be implicated in the pathogenesis of SSc, and if this pathway could represent a new therapeutic target in this orphan disease with no curative medicine. Skin biopsies from 11 patients and 10 controls were harvested, and skin fibroblasts were extracted. Experimental SSc was induced both in BALB/c and in nrf2-/- mice by daily intradermal injections of hypochloric acid. In addition, diseased BALB/c mice were treated with an nrf2 agonist, dimethyl fumarate, or placebo. A drop in nrf2 and target genes mRNA levels was observed in skin fibroblasts of SSc patients compared to controls. Moreover, the nrf2 pathway is also downregulated in skins and lungs of SSc mice. In addition, we observed that nrf2-/- mice have a more severe form of SSc with increased fibrosis and inflammation compared to wild-type SSc mice. Diseased mice treated with the nrf2 agonist dimethyl fumarate (DMF) exhibited reduced fibrosis and immune activation compared to untreated mice. The ex vivo treatment of skin fibroblasts from SSc mice with DMF restores GSH intracellular content, decreases ROS production and cell proliferation. These results suggest that the nrf2 pathway is highly dysregulated in human and SSc mice with deleterious consequences on fibrosis and inflammation and that Nrf2 modulation represents a therapeutic target in SSc.

PMID: 30177933 [PubMed - in process]

Exploring patient and family involvement in the lifecycle of an orphan drug: a scoping review.

Orphanet J Rare Dis. 2017 12 22;12(1):188

Authors: Young A, Menon D, Street J, Al-Hertani W, Stafinski T

Abstract
BACKGROUND: Patients and their families have become more active in healthcare systems and research. The value of patient involvement is particularly relevant in the area of rare diseases, where patients face delayed diagnoses and limited access to effective therapies due to the high level of uncertainty in market approval and reimbursement decisions. It has been suggested that patient involvement may help to reduce some of these uncertainties. This review explored existing and proposed roles for patients, families, and patient organizations at each stage of the lifecycle of therapies for rare diseases (i.e., orphan drug lifecycle).
METHODS: A scoping review was conducted using methods outlined by Arksey and O'Malley. To validate the findings from the literature and identify any additional opportunities that were missed, a consultative webinar was conducted with members of the Patient and Caregiver Liaison Group of a Canadian research network.
RESULTS: Existing and proposed opportunities for involving patients, families, and patient organizations were reported throughout the orphan drug lifecycle and fell into 12 themes: research outside of clinical trials; clinical trials; patient reported outcomes measures; patient registries and biorepositories; education; advocacy and awareness; conferences and workshops; patient care and support; patient organization development; regulatory decision-making; and reimbursement decision-making. Existing opportunities were not described in sufficient detail to allow for the level of involvement to be assessed. Additionally, no information on the impact of involvement within specific opportunities was found. Based on feedback from patients and families, documentation of existing opportunities within Canada is poor.
CONCLUSIONS: Opportunities for patient, family, and patient organization involvement exist throughout the orphan drug lifecycle. However, based on the information found, it is not possible to determine which opportunities would be most effective at each stage.

PMID: 29273068 [PubMed - indexed for MEDLINE]

A challenging case of calcific myonecrosis of tibialis anterior and hallucis longus muscles with a chronic discharging wound.

Int Wound J. 2018 Feb;15(1):170-173

Authors: Tan AM, Loh CYY, Nizamoglu M, Tare M

Abstract
The occurrence of calcific myonecrosis of the anterior compartment of the leg is rare. Common risk factors include a history of trauma, although little is known about the exact pathophysiology, latency period or triggering factors resulting in disease progression. Macroscopically, it begins with a single muscle being replaced by a fusiform calcified mass, which progresses peripherally. We present a rare case of a 7-year history of chronic discharging sinus overlying the site with protruding calcified muscle and discuss the senior author's wound management strategy and surgical considerations. The initial approach used dressing applications to reduce wound exudate while obtaining repeated imaging for disease progression comparison. Repeated CT scans showed significant disease progression from a single solitary amorphous soft tissue calcification to disseminated scattered calcified myonecrosis. In planning such surgeries, extensive debridement and temporary wound coverage is the first stage. Subsequent definitive coverage includes skin grafting of the remaining defect.

PMID: 29076298 [PubMed - indexed for MEDLINE]

Squamous cell carcinoma of the scrotum: the revisit of a rare disease.

ANZ J Surg. 2017 Oct;87(10):E161-E162

Authors: Phukan C, Abrol N, Kumar RM, Devasia A

PMID: 25766760 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/09/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/09/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

[Is "associativism" good for one's health? The case of rare diseases].

Cien Saude Colet. 2018 Feb;23(2):417-430

Authors: Barbosa RL, Portugal S

Abstract
Based on the question of an inspiring work - "Is the Market good for one's Health?", this paper poses a similar question, centered on "associativism" (belonging to a labor group or association) and the field of rare diseases. Starting from the research carried out in the scope of the Master's Degree in Sociology of the School of Economics of the University of Coimbra, this text puts into perspective the formulations created for the field of genetic conditions that, mainly, depart from a Eurocentric vision. The field of rare diseases is analyzed, identifying the roles, relationships and motivations of the different actors, namely, civil associations, pharmaceutical industry, academy, government, and families. The analysis highlights the preponderance of the market and the production of medicines, identifying a governance model - Utility Model of Care - in which the person who suffers and his/her family are left devoid of their subjectivity and transmuted into medication and market agents.

PMID: 29412400 [PubMed - indexed for MEDLINE]

[Family Therapeutic Trajectories: rare hereditary diseases involving long-term suffering].

Cien Saude Colet. 2018 Feb;23(2):369-380

Authors: Aureliano WA

Abstract
This article analyzes common elements in the trajectory of people affected by rare hereditary diseases in Brazil, focusing on the search for diagnosis and treatment, and the reproducibility in the family. Rare diseases affect 65 people in every 100 thousand. These are usually chronic and degenerative conditions, many incurable or without effective treatment. About 80% of rare diseases are genetic in origin and can be inherited. This fact has important implications for family health care policies, reproduction, and care for clinical conditions that, in some cases, spanned generations. To analyze the data, two theoretical axes are articulated: family and kinship studies, and analyzes of long-term suffering. The research investigated people affected by rare hereditary diseases and their families, in the political scenarios in which these actors circulate, such as patient associations, scientific congresses and public hearings. There is evidence of the need to build a continuous agenda on rare diseases in Brazil capable of effectively promoting universal and integral access of the affected persons to the public health system, and seeking for solutions to alleviate suffering that threatens the very continuity of the family.

PMID: 29412395 [PubMed - indexed for MEDLINE]

Self-report data as a tool for subtype identification in genetically-defined Parkinson's Disease.

Sci Rep. 2018 Aug 28;8(1):12992

Authors: Winslow AR, Hyde CL, Wilk JB, Eriksson N, Cannon P, Miller MR, Hirst WD

Abstract
Through a targeted recruitment 23andMe has collected DNA and patient-reported symptoms from more than 10,000 subjects reporting a physician-verified diagnosis of PD. This study evaluated the potential of self-report, web-based questionnaires to rapidly assess disease natural history and symptomology in genetically-defined PD populations. While average age-at-diagnosis was significantly lower in GBA mutation carriers compared to idiopathic PD, or iPD (idiopathic PD, defined as no GBA mutations and no LRRK2 G2019S mutation), there were no significant differences in symptoms. Conversely, LRRK2 G2019S carrier status significantly associated with reporting of milder daily symptoms of lightheadedness and several differences were observed at a false discovery rate < 0.1, including increased reporting of changes in walking as an initial symptom of disease, decreased reporting of lightheadedness upon standing, and milder symptoms related to daily functioning. The subclinical differences in symptoms reported by LRRK2 G2019S carriers suggest differences in underlying pathophysiology and/or disease progression in LRRK2 carriers compared to iPD. Importantly, we confirm previous findings in PD genetic subsets where disease characteristics were ascertained through clinical exam. Overall, these data support the effective use of self-report and genetic data to rapidly analyze information from a large disease population or difficult to identify genetic subgroups.

PMID: 30154511 [PubMed - in process]

[Solid pediatric tumors : A brief survey of the rarity cabinet].

Pathologe. 2017 Jul;38(4):278-285

Authors: Gürtl-Lackner B, Gisselsson-Nord D, Vujanic G

Abstract
Solid tumors in childhood are extremely rare entities, which are usually treated in specialized centers. Diagnosis and therapy are carried out according to a joint European protocol, whereby the pathological evaluation and therapy are carried out according to international guidelines. For the correct diagnosis and/or therapy of most tumors, analysis of specific genetic changes is mandatory; therefore, tumors have to be adequately sampled for parallel genetic analysis during the pathological work-up. A second opinion reference of the histopathological assessment is part of the international guidelines. Neuroblastomas, congenital mesoblastic nephromas and rhabdoid tumors are examples of solid tumors in childhood that are not restricted to one organ and occur exclusively during childhood.

PMID: 28643124 [PubMed - indexed for MEDLINE]

De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.

Am J Med Genet A. 2018 Aug 27;:

Authors: Wojcik MH, Okada K, Prabhu SP, Nowakowski DW, Ramsey K, Balak C, Rangasamy S, Brownstein CA, Schmitz-Abe K, Cohen JS, Fatemi A, Shi J, Grant EP, Narayanan V, Ho HH, Agrawal PB

Abstract
KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p.Gly546Ser, in the proband. This variant alters a highly conserved amino acid residue that is part of the phosphate-binding loop motif and motor-like domain and is deemed pathogenic by several in silico methods. Functional analysis of the variant protein in cultured cells revealed a reduction in the KIF26B protein's ability to promote cell adhesion, a defect that potentially contributes to its pathogenicity. Overall, KIF26B may play a critical role in the brain development and, when mutated, cause pontocerebellar hypoplasia with arthrogryposis.

PMID: 30151950 [PubMed - as supplied by publisher]

Esophageal metastasis of stem cell-subtype hepatocholangiocarcinoma: Rare presentation of a rare tumor.

World J Gastroenterol. 2018 Feb 21;24(7):870-875

Authors: Salimon M, Chapelle N, Matysiak-Budnik T, Mosnier JF, Frampas E, Touchefeu Y

Abstract
Hepatocholangiocarcinoma (cHCC-ICC) is a rare primary hepatic tumor defined by the presence of histological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Its prevalence ranges from 1%-5% of all primary liver cancers. We report the case of a 55-year-old cirrhotic male patient admitted to our university hospital for dysphagia, revealing a 10 cm lower-third esophageal metastasis of an unresectable cHCC-ICC with stem-cell features. Computed tomography and abdominal magnetic resonance imaging scans revealed multiple hepatic lesions combining features of both HCC and ICC, associated with synchronous bone metastasis. Histological and immunohistochemical analyses of biopsies from the esophageal lesion and the hepatic tumor confirmed the diagnosis of cHCC-ICC with a stem cell-subtype, according to the World Health Organization classification. After a multidisciplinary meeting, the patient was treated with chemotherapy. He received two cycles of a gemcitabine plus cisplatin regimen before bone progression, and he died 3 mo after the initial diagnosis.

PMID: 29467557 [PubMed - indexed for MEDLINE]

Ustekinumab treatment of pityriasis rubra pilaris: A report of five cases.

J Dermatol. 2018 Feb;45(2):202-206

Authors: Napolitano M, Lembo L, Fania L, Abeni D, Didona D, Didona B

Abstract
Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti-tumor necrosis factor agents. Recently, a role of the interleukin-23/T-helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult-onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult-onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15-month follow-up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first-line treatment for PRP patients refractory to conventional therapies.

PMID: 29080273 [PubMed - indexed for MEDLINE]

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/08/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/08/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Renal cell carcinoma in a horseshoe kidney: Report of a rare disease.

Niger Postgrad Med J. 2016 Oct-Dec;23(4):232-234

Authors: Tijani KH, Ojewola RW, Orakwe DE, Oliyide AE

Abstract
A horseshoe kidney (HSK) is the most common congenital renal fusion anomaly. HSKs are more likely than normal kidneys to have associated problems of stones, ureteropelvic junction obstruction, stasis and infection. However, they do not have an increased incidence of renal cell carcinoma when compared to normal kidneys. Due to its rarity, accurate diagnosis may be difficult. Of similar significance is the fact that problems may arise during surgery on these kidneys due to altered anatomy and aberrant blood supply. We report a case of HSK with a renal tumour in a 69-year-old woman and highlight our challenges in the management of the case. To the best of our knowledge, this is the first reported case of a tumour in an HSK in West Africa.

PMID: 28000646 [PubMed - indexed for MEDLINE]