Optimisation of botulinum toxin type a treatment for the management of Raynaud’s phenomenon using a dorsal approach: a prospective case series

Clinical Rheumatology - Raynaud’s phenomenon (RP) is a common condition and causes pain, paraesthesia, ulceration and gangrene. Botulinum toxin A (Btx-A) is effective when injected via a...     

Neonatal screening: from the ‘Guthrie age’ to the ‘genetic age’

Summary Newborn screening has ‘traditionally’ been performed to detect metabolic or endocrine diseases that are severe, frequent and treatable, according to criteria established in the late 1960s. Technological advances in laboratory testing over the past ten years open new possibilities. However, many new problems have to be explored before the establishment or expansion of a newborn screening programme. The purpose of this paper is to present some of the major problems that screening programmes will face in the near future. Competing interests: None declared     

Coincident Kikuchi-Fujimoto’s disease and adult-onset Still’s disease: report of a patient from an uncommonly affected population and case-directed systematic review

Clinical Rheumatology - Kikuchi-Fujimoto's disease (KFD) and adult-onset Still’s disease (AOSD) are rare idiopathic inflammatory conditions of unknown etiology. Ten prior instances of KFD...     

Myelomatous pleural effusion as an initial sign of multiple myeloma—a case report and review of literature

Objective

Discuss and improve the understanding of the clinical characters and diagnostic methods of myelomatous pleurisy, particularly of the patients with pleural effusion as an initial manifestation.

Background

A 53-year-old male, who had been misdiagnosed as tuberculous pleurisy in a local hospital, was diagnosed as multiple myeloma (MM) with pleural infiltration. We reviewed the literature on clinical manifestations, serum and pleural effusion characters, treatment and diagnostic options of this exceptionally rare presentation of MM.

Methods

We conducted a search of the published medical literature since 2000 in MEDLINE and PubMed using search criteria [(“pleural effusion” and “MM”) or “myelomatous pleural effusions”]. The search led to 64 case reports, and 16 cases with pleural effusion as an initial manifestation were included in this review. We have also searched for recent advances in diagnosis.

Results and conclusions

Myelomatous pleurisy is a rare complication of MM. Its clinical and laboratory findings are non-specific. Definitive diagnosis relies on the histopathology of pleural biopsy or pleural effusion. Thoracoscopic pleural biopsy is reliable, safe and effective. Chemotherapy is the mainstay of treatment for myelomatous pleural effusion. However, the response rate is low with an overall median survival time of 4 months.     

Development of multiple myeloma in a patient with chronic hepatitis C： A case report and review of the literature

An association between chronic hepatitis C virus (HCV) infection and essential mixed cryoglobulinaemia and non-Hodgkin lymphoma (NHL) has been suggested. However, a causative role of HCV in these conditions has not been established. The authors report a case of a 50 year-old woman with chronic hepatitis C (CHC) who has been followed up since 1998 due to a high viral load, genotype 1b and moderately elevated liver function tests (LFTs). Laboratory data and liver biopsy revealed moderate activity (grade: 5/18, stage: 1/6). In April 1999, one-year interferon therapy was started. HCV-RNA became negative with normalization of LFTs. However, the patient relapsed during treatment. In September 2002, the patient was admitted for chronic back pain. A CT examination demonstrated degenerative changes. In March 2003, multiple myeloma was diagnosed (IgG-kappa, bone marrow biopsy: 50% plasma cell infiltration). MRI revealed a compression fracture of the 5th lumbar vertebral body and an abdominal mass in the right lower quadrant, infiltrating the canalis spinalis. Treatment with vincristine, adriamycin and dexamethasone (VAD) was started and bisphosphonate was administered regularly. In January 2004, after six cycles of VAD therapy, the multiple myeloma regressed. Thalidomide, as a second line treatment of refractory multiple myeloma (MM) was initiated, and followed by peginterferon-a2b and ribavirin against the HCV infection in June. In June 2005, LFTs returned to normal, while HCV-RNA was negative, demonstrating an end of treatment response. Although a pathogenic role of HCV infection in malignant lymphoproliferative disorders has not been established, NHL and possibly MM may develop in CHC patients, supporting a role of a complex follow-up in these patients.     

Pituicytoma in a patient with Cushing’s disease: case report and review of the literature

There are scant prospective studies defining improvements in critical outcome measures with hormone replacement in hypopituitarism secondary to brain injury. We review the tests of cognition and physical function and summarize their use for subjects that are deficient in anterior hormone production during anterior pituitary hormone replacement in brain injury and propose these as the minimal tests that are feasible for a physician to perform in a clinical setting. We summarize the studies conducted to assess outcome measures after brain injury and also report preliminary findings for improvements in cognition and physical function in subjects with brain injury and GH deficiency.     

Pituicytoma in a patient with Cushing’s disease: case report and review of the literature

Pituicytoma is an exceptionally rare low-grade glioma (WHO grade I) of the neurohypophysis and infundibulum. We are reporting the case of a 48-year-old man who presented with severe Cushing′s syndrome. Endocrinological evaluation unequivocally confirmed pituitary-dependent Cushing’s syndrome (=Cushing’s disease). Cranial MR-imaging displayed a conspicuous area in the dorsal and basal pituitary gland and a minimal bulging of the pituitary gland paramedian of the pituitary stalk on the right side. Transsphenoidal inspection revealed a small tumor in the basal and dorsal pituitary gland. Surprisingly, the definite postoperative histopathological diagnosis of the removed tumor was pituicytoma and not pituitary adenoma. Hence, the microadenoma responsible for Cushing’s disease was not yet removed and persistent hypercortisolism necessitated transsphenoidal re-operation. During re-operation, hemihypophysectomy was performed on the right side. The non-tumorous specimen of the adeno-hypophysis showed signs of Crooke’s hyalinization consistent with Cushing’s disease. Undetectable postoperative ACTH- and cortisol levels provided clear evidence that the underlying ACTH-source was successfully removed during re-operation. Coincidence of pituicytoma and pituitary-dependent Cushing’s disease has not previously been reported.

     

DIY artificial pancreas: A narrative of the first patient and the physicians’ experiences from India

Background aimsFrustrated with the slow-pace of innovations in diabetes technologies, the type 1 diabetes community have started closing the loop by themselves to automate insulin delivery. While the regulatory and ethical concerns over the systems are still high, these have contributed to enhanced glycemic control characterized by improved estimated HbA1c and time-in-range above 90% as for many users. Our objective is to provide the real-world experience of the first successful patient from India on the Do-It-Yourself Artificial Pancreas (DIYAP) and the perspective of her physicians.MethodsA narrative recounting of a personal experience on DIYAP. The patient completed a Hypoglycemia Fear Survey II and Diabetes Quality of Life instrument before and after looping.ResultsThe patient emphasized the personal/social benefits and the concerns of using the system. Looping has produced a clinically meaningful difference in the quality of life, better sleep patterns, and reduced the disease management burden. We also highlighted the relevant perspectives of the physicians to give deeper insights into the aspect.ConclusionThe patient highlighted better time-in-range, negligible time spent in hypoglycemia, and superior Quality of Life. Globally, more and more patients are adopting this technology; therefore, real-life patient stories will enlighten the medical community.     

Tocilizumab for the treatment of adult-onset Still’s disease: results from a case series

Adult-onset Still’s disease (AOSD) is a chronic inflammatory disease of unknown etiology which commonly affects young adults. Treatment of AOSD patients includes nonsteroidal anti-inflammatory drugs, corticosteroids, and DMARDs. Interleukin (IL)-6 blockade is an attractive therapeutic option for AOSD because this cytokine contributes to the pathogenesis of major AOSD symptoms. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that blocks the effects of IL-6. Preliminary results of TCZ in AOSD have been promising. Here, we reported our experience evaluating both the safety and the efficacy of 12 months therapy with TCZ in 11 patients with AOSD refractory to corticosteroids and MTX therapy, followed for 18 months, including the first 12 months of active treatment and the last 6 months to evaluate the activity of the disease when the treatment was discontinued. The main outcome measures were the European League Against Rheumatism (EULAR) improvement criteria and improvement of systemic symptoms at the 3, 6, 12, and 18-months follow-up periods. Our patients rapidly responded and experienced a sustained clinical remission over time during active treatment. Disease Activity Score 28 decreased from 5.62 (3.75–8.28) [median (range)] at baseline to 1.61(0.49–3.5) at month 12. EULAR remission was achieved in 81.82 % at 12 months. Tender joint and swollen joint counts displayed a progressive reduction during active therapy study period. During treatment, we observed a resolution of fever in our AOSD patient. In conclusion, TCZ might represent a suitable option for the therapy of refractory AOSD patients.     

From the Cover: Developmental origins of the world’s largest flowers,Rafflesiaceae

Rafflesiaceae, which produce the world’s largest flowers, have captivated the attention of biologists for nearly two centuries. Despite their fame, however, the developmental nature of the floral organs in these giants has remained a mystery. Most members of the family have a large floral chamber defined by a diaphragm. The diaphragm encloses the reproductive organs where pollination by carrion flies occurs. In lieu of a functional genetic system to investigate floral development in these highly specialized holoparasites, we used comparative studies of structure, development, and gene-expression patterns to investigate the homology of their floral organs. Our results surprisingly demonstrate that the otherwise similar floral chambers in two Rafflesiaceae subclades, Rafflesia and Sapria, are constructed very differently. In Rafflesia, the diaphragm is derived from the petal whorl. In contrast, in Sapria it is derived from elaboration of a unique ring structure located between the perianth and the stamen whorl, which, although developed to varying degrees among the genera, appears to be a synapomorphy of the Rafflesiaceae. Thus, the characteristic features that define the floral chamber in these closely related genera are not homologous. These differences refute the prevailing hypothesis that similarities between Sapria and Rafflesia are ancestral in the family. Instead, our data indicate that Rafflesia-like and Sapria-like floral chambers represent two distinct derivations of this morphology. The developmental repatterning we identified in Rafflesia, in particular, may have provided architectural reinforcement, which permitted the explosive growth in floral diameter that has arisen secondarily within this subclade.It has been long recognized that parasitism elicits fundamental changes to an organism’s body plan (1, 2). Similarly, extreme changes in body size can result in dramatic morphological modifications, which in some cases rise to the level of what we term “novelty’” (3–5). Either of these circumstances can pose challenges to understanding structural homology. One lineage that exhibits both complications is the holoparasitic plant family Rafflesiaceae, which produces the world’s largest flowers. Despite their fame, however, the developmental basis of these giants has remained a mystery for nearly two centuries (6, 7). Their floral structure, in particular, is highly modified with respect to most angiosperms, so much so that confusion over their flowers has resulted in Rafflesiaceae-centric terminology to evade statements of homology. This uncertainty has obscured our understanding of their evolutionary origin, which until recently has been unknown (8–10).Most members of the family possess a large, bowl-shaped floral chamber [sometimes referred to as a chamber blossom by pollination biologists (11, 12)]. The floor and walls of this chamber are formed by a perianth tube and the roof is defined by an organ called the diaphragm (Fig. 1 and Fig. S1 A and C–E). The opening of the diaphragm serves as the entrance for carrion fly pollinators (13, 14). The chamber is in turn surrounded by a series of attractive sterile organs, termed perianth lobes (Fig. 1 and Fig. S1 A, C–E, and G–K). The central part of the chamber accommodates the central column, which expands distally to form a disk bearing the reproductive organs (Fig. 1 and Fig. S1). Like their closest relatives, Euphorbiaceae, the flowers of Rafflesiaceae are typically unisexual (9). In female flowers, a stigmatic belt forms around the underside of the reproductive disk (13); in male flowers this is where the stamens are borne.Open in a separate windowFig. 1.Gross morphology, longitudinal sections, and accepted phylogenetic relationships of Rafflesiaceae. Rafflesia (A) and Sapria (C) exhibit floral chambers, defined by a diaphragm, where the central reproductive column resides. The central column of Rhizanthes (B) is exposed because no floral chamber is formed. (Scale bars, ∼2 cm.) Photo credits: (A) D. Boufford, (B) C.C.D., (C) L.A.N.Each of the three genera of Rafflesiaceae produces flowers that vary on this general theme. Rafflesia and Sapria have a similar floral architecture, but differ in their perianths: Rafflesia has one whorl of five perianth lobes (Fig. 1A) and Sapria has two whorls (Fig. 1C), each with five similar lobes. Because of the striking similarity in floral morphology of these two genera, which represent the bulk of species diversity in the family, their floral chambers have been assumed to have originated once in the common ancestor of Rafflesiaceae (15) (Fig. 1). The exception is the species-poor clade Rhizanthes, which lacks the floral chamber found in most Rafflesiaceae (16) (Fig. 1B). Rhizanthes has 16 similar perianth lobes and does not form a diaphragm or chamber closure as in Rafflesia and Sapria. The perianth lobes in Rhizanthes also differ considerably in morphology: they are much narrower, have elaborate hairy “pads,” and terminate with distinct tail-like appendages (Fig. 1 and Fig. S1 G–K). Based on its more nested phylogenetic placement within the family, it has been assumed that the morphology of Rhizanthes is uniquely derived (15). The unusual floral organs of Rafflesiaceae pose a serious challenge to understanding their homology and, thus, their evolution.Like so many branches in the Tree of Life, Rafflesiaceae are not amenable to traditional genetic manipulation, even less so than most plants. These holoparasites grow vegetatively inside their hosts and lack obvious leaves, stems, and roots. The plants have never been successfully propagated, and do not occur outside of their host range in the rainforests of Southeast Asia. Under these circumstances, only multiple independent lines of inquiry can be used to understand the floral structure and evolution of these charismatic plants, including comparative structural, developmental, and gene-expression data. In terms of this last source of data, the ABC model of floral development provides a predictive framework for understanding the identities of the floral organs of Rafflesiaceae (17, 18). The model involves three gene activities: A activity alone specifies sepal identity, A+B define petals, B+C confer stamen identity, and C determines carpel identity. Although it has been recognized that some aspects of the ABC model do not apply to all angiosperms (19), the specification of petal, stamen, and carpel identity by B- and C-class genes is generally conserved in core eudicots (20). In general, great care must be taken when using gene-expression patterns as criteria for establishing homology (21); however, when such correlative data are combined with explicit phylogenetic and developmental data, this approach has been shown to provide critical insights into organ homology (e.g., ref. 22). Along these lines, we cloned homologs of the ABC class genes, which largely belong to the pan-eukaryotic MADS-box (after the four founding members of the family: MCM1, AGAMOUS, DEFICIENS, and SRF) gene family (20), from Rafflesiaceae and studied their expression in different floral organs. We complemented these analyses with an investigation of floral organ initiation and development in all three genera in the family.Our analyses surprisingly demonstrate that the otherwise similar floral chambers in Rafflesia and Sapria are constructed very differently. In Rafflesia, the diaphragm is derived from the petal whorl, whereas normal petals are absent. In contrast, in Sapria the diaphragm is derived from elaboration of a unique ring structure located between the perianth and the stamen whorl. This structure is analogous to sterile organs that have been independently derived in other angiosperms, such as the trumpet in daffodils (23) and the corona in passionflowers (24). The structure is not present in the closest relatives of Rafflesiaceae, and is elaborated to varying degrees in all three genera of Rafflesiaceae. Thus, the structures that define these similar floral chambers are not homologous. In Rhizanthes, which lacks a diaphragm, a derivative of the ring primordium appears to be adnate to the perianth. The development of this organ is more similar to that of Sapria, and is likely a shared symplesiomorphic feature in these two genera. These differences in construction among the three genera refute the simplistic scenario in which the similarities between Sapria and Rafflesia are interpreted as ancestral in the family.     

Raynaud’s phenomenon and blood rheology: comments on the article “Raynaud’s phenomenon—an update on diagnosis,classification and management”

Clinical Rheumatology -     

Diagnosis and management of acromegaly: the patient’s perspective

Purpose

Early diagnosis is a success factor for the prevention of long-term comorbidity and premature death in patients with acromegaly, but large-scale data on the diagnostic process and disease management are scarce. Therefore, we aimed to evaluate the diagnostic process, implementation of treatment and changes in life situation in patients with acromegaly, focusing on sex-specific differences.

Methods

Non-interventional patient-reported outcome study. 165 patients with clinically and biochemically proven acromegaly were questioned about the diagnostic process and utilization of health care by means of a self-developed standardized postal survey including questions on acromegaly symptoms experienced before diagnosis, number and specialty of consulted doctors, time to diagnosis and aftercare.

Results

The diagnostic process took 2.9 (SD 4.53) years, during which 3.4 (SD 2.99) physicians were consulted. Women waited longer [4.1 (SD 5.53) years] than men [1.6 (SD 2.69) years; p = 0.001] for the correct diagnosis, and consulted more doctors in the process [4.0 (SD 2.99) vs. 2.7 (SD 2.84) doctors, p < 0.001, respectively]. In 48.5 % of patients, acromegaly was diagnosed by an endocrinologist (men: 45.1 %; women: 52.4 %). Overall disease duration from symptom onset until last surgery was 5.5 (SD 6.85) years, with no sex differences. A change in employment status was the most commonly reported event after diagnosis and a quarter of the patients stated that the illness had changed their lives.

Conclusions

Our findings confirm the urgent need to increase awareness of the clinical manifestation of acromegaly to facilitate an earlier diagnosis of the disease and to provide diagnostic equality across the sexes.

     

Takayasu’s arteritis: case report of a patient with recurrent subclavian steal syndrome

Takayasus arteritis is a chronic inflammatory disease of unknown origin in which cell-mediated inflammation involves large arteries progressing from the adventitia to the intima, until the lumen of the vessel is narrowed. Here we report a case of a 48-year-old female patient who was diagnosed with Takayasus arteritis 6 years ago. At that time, because of severe involvement of both the right and left carotid arteries, she underwent application of a Hemashield vascular prosthesis, including the ascending aorta, left common carotid artery, and right common carotid artery. Due to the fact that there were also bilateral subclavian artery stenoses, the application of the prosthesis induced bilateral subclavian steal syndrome. This year she developed stenosis of the prosthesis and the bilateral subclavian steal syndrome disappeared until she underwent percutaneous transluminal angioplasty, which restored cerebral flow through the carotid arteries after which the subclavian steal syndrome reappeared.     

Purtscher’s-like retinopathy as an initial presentation of adult-onset Still’s disease: a case report and review of the literature

Adult-onset Still’s disease is a multisystem inflammatory disorder of unknown etiology and is characterized by high, spiking fever, arthritis, evanescent maculopapular rash, myalgia, serositis, leukocytosis, and involvement of various organs including the eyes. The ocular manifestations have been described including orbital pseudotumor, ptosis, and diplopia with orbital pain but never Purtscher’s-like retinopathy. We describe a 21-year-old male patient with adult-onset Still’s disease who developed the Purtscher’s-like retinopathy. To our knowledge, this is the first reported adult-onset Still’s disease patient with Purtscher’s-like retinopathy as the initial presentation.     

Malignant peripheral nerve sheath tumor of the colon in a patient with von Recklinghausen’s disease: report of a case

Malignant peripheral nerve sheath tumor (MPNST) arising from the colon is an extremely rare clinical entity. We report one such case of an adult female with neurofibromatosis type I who presented with pain and a lump in her abdomen. A computed tomographic scan revealed a 10 × 8-cm mass in the splenic flexure of her colon that was compressing its lumen, but the results of a colonoscopy were normal. Segmental resection of the left colon was performed based on the clinical possibility of gastrointestinal stromal tumor. However, on histopathological examination and immunohistochemical staining, the final diagnosis came out to be MPNST. This case highlights that, although rare, the possibility of MPNST should be considered when dealing with extramucosal colonic wall tumors.     

‘Personalizing’ shorter regimens: Need of the hour

IntroductionThe launch of injectable shorter regimens under Programmatic Management of Drug Resistant Tuberculosis (PMDT) guidelines 2017 under Revised National Tuberculosis Control Program (RNTCP) was a welcome step as it decreased the duration of treatment significantly in Drug Resistant Tuberculosis (DRTB) patients.The objective of the present study was to evaluate the treatment outcomes of patients started on injectable shorter regimens from March 2018 to May, 2019.MethodsRetrospective study which scrutinized medical records of 85 patients started on injectable shorter regimen was conducted. Necessary information on possible patient and disease related predicting factors like age, gender, weight, HIV status, presence of diabetes mellitus (DM), anemia, gap between diagnosis and initiation of treatment, duration of intensive phase (IP) and time of sputum conversion was retrieved, and analyzed for possible association with treatment outcomes.Results56.5% had successful treatment outcomes. Age, gender, BMI, diabetic/anemic status and gap between diagnosis and initiation of treatment had no statistically significant relationship with the final outcomes. Duration of IP, sputum conversion and time of outcome during the course of illness emerged as significant factors in successful outcomes.ConclusionThe injectable shorter regimens were suitable for a variety of population irrespective of demographic disparities. Patients need to be followed closely as microbiological parameters serve as early indicators of unsuccessful outcomes. These regimens can serve as an alternate choice in patients not tolerating the all oral shorter Bedaquiline containing shorter regimen. Similar such options with combinations of different drugs for individualizing treatment regimens is the need of the hour.