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Journal of Medical Case Reports Oct 2016Scleroderma is a chronic connective tissue disorder with unknown etiology. It is characterized by excessive deposition of extracellular matrix in the connective tissues...
BACKGROUND
Scleroderma is a chronic connective tissue disorder with unknown etiology. It is characterized by excessive deposition of extracellular matrix in the connective tissues causing vascular disturbances which can result in tissue hypoxia. These changes are manifested as atrophy of the skin and/or mucosa, subcutaneous tissue, muscles, and internal organs. Such changes can be classified into two types, namely, morphea (localized) and diffuse (systemic). Morphea can manifest itself as hemifacial atrophy (Parry-Romberg syndrome) although this remains debatable. Hence, we present a case of morphea, associated with Parry-Romberg syndrome, and a second case with the classical signs of progressive systemic sclerosis.
CASE PRESENTATION
Case one: A 20-year-old man of Dravidian origin presented to our out-patient department with a complaint of facial asymmetry, difficulty in speech, and loss of taste sensation over the last 2 years. There was no history of facial trauma. After physical and radiological investigations, we found gross asymmetry of the left side of his face, a scar on his chin, tongue atrophy, relative microdontia, thinning of the ramus/body of his mandible, and sclerotic lesions on his trunk. Serological investigations were positive for antinuclear antibody for double-stranded deoxyribonucleic acid and mitochondria. A biopsy was suggestive of morphea. Hence, our final diagnosis was mixed morphea with Parry-Romberg syndrome. Case two: A 53-year-old woman of Dravidian origin presented to our out-patient department with a complaint of gradually decreasing mouth opening over the past 7 years. Her medical history was noncontributory. On clinical examination, we found her perioral, neck, and hand skin to be sclerotic. Also, her fingers exhibited bilateral telangiectasia. An oral examination revealed completely edentulous arches as well as xerostomia and candidiasis. Her serological reports were positive for antinuclear antibodies against centromere B, Scl-70, and Ro-52. A hand and wrist radiograph revealed acro-osteolysis of the middle finger on her right hand. Hence, our final diagnosis was progressive systemic sclerosis.
CONCLUSION
Through this article, we have tried to emphasize the importance of a general examination when diagnosing rare systemic diseases such as scleroderma and the role of the general dentist when caring for such patients, even though they can be quite rare in general practice.
Topics: Dentistry; Facial Hemiatrophy; Female; Humans; Male; Middle Aged; Physical Examination; Rare Diseases; Referral and Consultation; Rheumatology; Scleroderma, Localized; Young Adult
PubMed: 27776552
DOI: 10.1186/s13256-016-1086-1 -
American Journal of Human Genetics Dec 2018We have investigated a distinct disorder with progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion...
We have investigated a distinct disorder with progressive corneal neovascularization, keloid formation, chronic skin ulcers, wasting of subcutaneous tissue, flexion contractures of the fingers, and acro-osteolysis. In six affected individuals from four families, we found one of two recurrent variants in discoidin domain receptor tyrosine kinase 2 (DDR2): c.1829T>C (p.Leu610Pro) or c.2219A>G (p.Tyr740Cys). DDR2 encodes a collagen-responsive receptor tyrosine kinase that regulates connective-tissue formation. In three of the families, affected individuals comprise singleton adult individuals, and parental samples were not available for verification of the de novo occurrence of the DDR2 variants. In the fourth family, a mother and two of her children were affected, and the c.2219A>G missense variant was proven to be de novo in the mother. Phosphorylation of DDR2 was increased in fibroblasts from affected individuals, suggesting reduced receptor autoinhibition and ligand-independent kinase activation. Evidence for activation of other growth-regulatory signaling pathways was not found. Finally, we found that the protein kinase inhibitor dasatinib prevented DDR2 autophosphorylation in fibroblasts, suggesting an approach to treatment. We propose this progressive, fibrotic condition should be designated as Warburg-Cinotti syndrome.
Topics: Adult; Amino Acid Sequence; Child; Child, Preschool; Collagen; Connective Tissue Diseases; Discoidin Domain Receptor 2; Female; Fibroblasts; Humans; Middle Aged; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Sequence Alignment; Signal Transduction
PubMed: 30449416
DOI: 10.1016/j.ajhg.2018.10.013 -
Cureus Mar 2024Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is an uncommon autosomal recessive disorder caused by a mutation in the uroporphyrinogen III...
Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is an uncommon autosomal recessive disorder caused by a mutation in the uroporphyrinogen III synthase gene. This mutation results in reduced enzyme levels in heme synthesis and the accumulation of pathogenic porphyrin isomers, uroporphyrin I and coproporphyrin I, leading to the clinical manifestations of CEP. Typically, CEP manifests shortly after birth with severe cutaneous photosensitivity, blistering, ulceration, and scarring. Erythrodontia, acro-osteolysis, and skeletal abnormalities are frequently present in conjunction with it. It can even manifest in utero as hydrops fetalis, with pink or red diaper staining as an early diagnostic clue. In this case, we present a 17-year-old male with complaints of discharge over the left foot, blisters upon sunlight exposure, extensive mottled pigmentation, excessive facial hair, mutilated fingers, and verrucous growth over the toes. Using a Wood's lamp revealed pink fluorescence of teeth and ulcers on the foot. Laboratory investigations demonstrated anemia, leukocytopenia, thrombocytopenia, and elevated urine uroporphyrin 1 and coproporphyrin 1 levels. Current treatment approaches include sun protection to avoid further skin damage, beta-carotene to reduce oxidative stress, and blood transfusions to manage anemia. Stem cell transplantation remains the sole curative therapy for this exceedingly rare condition. This case report underscores the rarity and complexity of CEP and emphasizes the challenges in its management.
PubMed: 38576642
DOI: 10.7759/cureus.55558 -
Experimental and Therapeutic Medicine Nov 2016Acro-osteolysis, or bony resorption of the terminal digital tufts, is a well-recognized, but under-researched, feature of systemic sclerosis. The mechanisms that...
Acro-osteolysis, or bony resorption of the terminal digital tufts, is a well-recognized, but under-researched, feature of systemic sclerosis. The mechanisms that disturbs local homeostatic balance of bone formation and resorption in favor of osteoclast activation and pathological bone loss remain to be established. Vascular alterations and reduced capillary density impair tissue oxygenation in systemic sclerosis, and the resulting hypoxia might contribute directly to the disease progression. In this paper we summarize the current evidence for hypoxia as the common pathophysiological denominator of digital vasculopathy and enhanced osteoclastic activity in systemic sclerosis-associated acroosteolysis. The hypoxia-inducible transcription factor HIF-1α and VEGF signaling has a critical role in regulating osteoclastic bone-resorption and angiogenesis, and increased osteoclastogenesis and higher VEGF levels may contribute to acroosteolysis in systemic sclerosis. The cells of the osteoblast lineage also have important roles in angiogenic-osteogenic coupling. The research in this field might help limiting the disability associated with the disease.
PubMed: 27882179
DOI: 10.3892/etm.2016.3782 -
Yonsei Medical Journal May 2011Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more...
Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.
Topics: Acro-Osteolysis; Adult; Bone Density Conservation Agents; Diphosphonates; Female; Hajdu-Cheney Syndrome; Humans; Imidazoles; Osteoporosis; Zoledronic Acid
PubMed: 21488202
DOI: 10.3349/ymj.2011.52.3.543 -
ACR Open Rheumatology May 2023
PubMed: 36988894
DOI: 10.1002/acr2.11541 -
The Journal of Biological Chemistry Dec 2021Notch2 mice, which harbor a mutation replicating that found in Hajdu-Cheney syndrome, exhibit marked osteopenia because of increased osteoclast number and bone...
Notch2 mice, which harbor a mutation replicating that found in Hajdu-Cheney syndrome, exhibit marked osteopenia because of increased osteoclast number and bone resorption. Hairy and enhancer of split 1 (HES1) is a Notch target gene and a transcriptional modulator that determines osteoclast cell fate decisions. Transcript levels of Hes1 increase in Notch2 bone marrow-derived macrophages (BMMs) as they mature into osteoclasts, suggesting a role in osteoclastogenesis. To determine whether HES1 is responsible for the phenotype of Notch2 mice and the skeletal manifestations of Hajdu-Cheney syndrome, Hes1 was inactivated in Ctsk-expressing cells from Notch2 mice. Ctsk encodes the protease cathepsin K, which is expressed preferentially by osteoclasts. We found that the osteopenia of Notch2 mice was ameliorated, and the enhanced osteoclastogenesis was reversed in the context of the Hes1 inactivation. Microcomputed tomography revealed that the downregulation of Hes1 in Ctsk-expressing cells led to increased bone volume/total volume in female mice. In addition, cultures of BMMs from Ctsk;Hes1 mice displayed a decrease in osteoclast number and size and decreased bone-resorbing capacity. Moreover, activation of HES1 in Ctsk-expressing cells led to osteopenia and enhanced osteoclast number, size, and bone resorptive capacity in BMM cultures. Osteoclast phenotypes and RNA-Seq of cells in which HES1 was activated revealed that HES1 modulates cell-cell fusion and bone-resorbing capacity by supporting sealing zone formation. In conclusion, we demonstrate that HES1 is mechanistically relevant to the skeletal manifestation of Notch2 mice and is a novel determinant of osteoclast differentiation and function.
Topics: Animals; Cell Differentiation; Female; Hajdu-Cheney Syndrome; Mice; Mice, Inbred C57BL; Mutation; Osteoclasts; Receptor, Notch2; Signal Transduction; Transcription Factor HES-1
PubMed: 34742737
DOI: 10.1016/j.jbc.2021.101376 -
Annals of the Rheumatic Diseases Aug 2006The osteoarticular and soft tissue structures of the hand may be involved in systemic sclerosis (SSc), causing functional disability.
BACKGROUND
The osteoarticular and soft tissue structures of the hand may be involved in systemic sclerosis (SSc), causing functional disability.
OBJECTIVE
To assess radiological hand features in a cross sectional study of SSc patients and in controls.
METHODS
Hand radiology was done systematically in patients with SSc seen over a two year period and in unselected controls with rheumatoid arthritis or digital trauma. Two independent investigators blind to the diagnosis carried out the radiological assessment.
RESULTS
120 consecutive SSc patients (median (range) age, 56.5 (20 to 90) years; disease duration, 6 (0 to 42) years) and 42 controls (22 with rheumatoid arthritis and 20 with digital trauma) were studied. Radiological abnormalities in SSc patients included erosion (21%), joint space narrowing (28%), arthritis (defined by concomitant erosion and joint space narrowing) (18%), radiological demineralisation (23%), acro-osteolysis (22%), flexion contracture (27%), and calcinosis (23%). In univariate and multivariate analysis, the resorption of distal phalanges was significantly associated with digital ulcers, extra-articular calcification, and pulmonary arterial hypertension; flexion contracture was associated with the diffuse cutaneous form and high HAQ (Health Assessment Questionnaire) disability score. Calcinosis was most often seen in patients with digital ulcers, but was similarly observed in patients with the diffuse or limited cutaneous subtypes.
CONCLUSIONS
Flexion contracture was associated with disability and occurred in patients with the diffuse cutaneous subtype of SSc, consistent with the tendency towards fibrosis and functional impairment of this subtype. Calcinosis and acro-osteolysis were both associated with vascular complications, highlighting a potential role of vascular injury in such lesions.
Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Calcinosis; Case-Control Studies; Cross-Sectional Studies; Female; Finger Injuries; Hand Joints; Humans; Hypertension, Pulmonary; Male; Middle Aged; Prospective Studies; Radiography; Scleroderma, Systemic; Skin Ulcer
PubMed: 16414976
DOI: 10.1136/ard.2005.044602 -
International Journal of Environmental... Jun 2022Hajdu-Cheney syndrome is a rare genetic disease. Its main features include phenotypic variability, age-dependent progression and the presence of acroosteolysis of the...
Hajdu-Cheney syndrome is a rare genetic disease. Its main features include phenotypic variability, age-dependent progression and the presence of acroosteolysis of the distal phalanges and generalized osteoporosis, which have significant disabling potential. Currently, there is no effective curative treatment, so nursing care is essential to ensure the maintenance of the quality of life of these patients. The main objective of this study was to establish a specific standardized nursing care plan using the NANDA-NIC-NOC taxonomy. The application of a care plan as such would improve the quality of life of patients affected by this rare disease, will contribute to increasing healthcare professionals' knowledge on this matter and will support future studies on this disease.
Topics: Acro-Osteolysis; Hajdu-Cheney Syndrome; Humans; Osteoporosis; Patient Care Planning; Quality of Life; Rare Diseases
PubMed: 35742738
DOI: 10.3390/ijerph19127489 -
Arthritis & Rheumatology (Hoboken, N.J.) Jan 2019
Topics: Acro-Osteolysis; Adult; Arthritis; Autoantibodies; Calcinosis; Contracture; DNA Topoisomerases, Type I; Hand Joints; Humans; Immunologic Factors; Lung Diseases, Interstitial; Male; Radiography; Raynaud Disease; Rituximab; Scleroderma, Diffuse
PubMed: 30221850
DOI: 10.1002/art.40723