Macrocephaly and Finger Changes: A Narrative Review.

Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.

Osteogenesis imperfecta and rheumatoid arthritis: connective issues.

The coexistence of osteogenesis imperfecta and inflammatory arthritis has been very rarely described. Nevertheless, systemic inflammation has been found in osteogenesis imperfecta. The COL1A1 mutations may affect collagen synthesis as well as post-translational modifications, extracellular matrix interactions, and receptor-mediated signaling. Major collagen binding ligands forming the interactome, such as cytokines, cell adhesion molecules, matrix metalloproteinases, proteoglycans, and other molecules, are autoimmunity targets involved in rheumatoid arthritis pathogenesis. Cross-talk between bone remodeling and inflammatory pathways involving osteoclasts is important in osteogenesis imperfecta and rheumatoid arthritis. In osteogenesis imperfecta, the structural abnormalities and repeated traumatism, including fractures, could activate locally the innate immunity and trigger arthritis, similar to post-traumatic arthritis. Currently, the therapy of osteogenesis imperfecta is a suboptimally met need. Understanding the complex putative pathogenic links between osteogenesis imperfecta and inflammatory arthritis could hopefully lead to new therapeutic targets. Raising awareness regarding a possible association between osteogenesis imperfecta and arthritis could help improve the quality of life in these patients.

Case Report: Anti-N-Methyl-D-Aspartate Receptor Encephalitis Manifesting With an Isolated Psychiatric Episode and Normal Ancillary Tests.

The majority of patients with anti-N-Methyl-D-Aspartate receptor (NMDAR) encephalitis present with psychiatric symptoms and subsequently develop neurological features. However, isolated psychiatric episodes occur in <5% of affected individuals, less frequent at disease onset (<1%) compared to relapse (4%). We report the case of a previously healthy 24-year-old female who presented with psychotic symptoms and behavioral alterations. Despite therapy, she showed no improvement and subsequently developed catatonic features. While the ancillary tests were normal, the clinical warning signs raised the suspicion of anti-NMDAR encephalitis which we later confirmed. Given its strong association with underlying tumors, we screened the patient and found an ovarian teratoma. Once removed, the patient displayed a substantial improvement in the mental status. Besides being extremely rare, this case illustrates the need to maintain clinical suspicion of anti-NMDAR encephalitis even in the absence of neurological features or paraclinical anomalies.

Osteogenesis imperfecta and rheumatoid arthritis: is there a link?

We present the cases of a mother and daughter with osteogenesis imperfecta, also diagnosed later with rheumatoid arthritis. In our patients finding and treating the over-imposed arthritis improved the joint pain initially attributed to osteogenesis imperfecta. Exploring joint inflammation in this setting could help ease the disease burden. PURPOSE: Osteogenesis imperfecta (OI) is a rare hereditary disease evolving with recurrent fractures upon minor trauma, blue sclerae, and hearing loss. Although inflammation was not generally considered a feature of the disease, systemic inflammation was recently reported in children with OI and in murine models of OI. METHOD: We present the cases of a mother and a daughter with OI, without a personal or family history of autoimmune diseases, who were also diagnosed with rheumatoid arthritis seropositive for anti-cyclic citrullinated peptide autoantibodies and rheumatoid factor. RESULTS: The genetic tests identified in both patients a deletion in COL1A1 gene (c.3399del, p.Ala1134Profs*105), not previously reported, not present in population databases, creating a premature translational stop signal in the COL1A1 gene in the collagen I major ligand binding region 3. In our patients finding and treating the over-imposed arthritis improved the joint pain initially attributed to OI. Possible pathogenic links between OI and RA are discussed. CONCLUSION: The prevalence of joint inflammation in OI is unknown and may be underestimated. As musculoskeletal involvement affects the quality of life in most OI patients, exploring this relation may help ease the disease burden.

Posttraumatic hip bulging mimicking an abscess in a patient with hip prosthesis: the role of ultrasonography.

A 48-yr old female patient, with stage 4 rheumatoid arthritis, who had undergone multiple joint prostheses including four arthroplasties of the left hip, presented for a sudden-onset large bulge on the left thigh, after a minor local injury. Orthopedic examination and radiography excluded fractures. Ultrasonography revealed a large mixed hypo- and hyperechoic collection,with no Doppler signal, but with comet tail artifacts. Repeated cultures from the collection were negative. Fluid analysis revealed increased quantities of titanium and cobalt. The sudden-onset deformity and fluid collection were in favor of a shear lesion (Morel-Lavallée). The new collection communicated with a previously asymptomatic periprosthetic aseptic abscess, mimicking an infection. To our knowledge, Morel-Lavallée shear lesions have not been described in patients with hip prostheses. Their presence may add to the difficulties of ruling out silent infections in such patients. Ultrasonography is a very effective method for the diagnosis and follow-up of collections in this setting.

Tracheal enlargement or Mounier-Kuhn syndrome in giant cell arteritis: a possible causal association with therapeutic implications.

Giant cell arteritis (GCA) is a large-vessel vasculitis with rarely described respiratory initial manifestations. We report such a case presenting with hoarseness, stridor, cough and dyspnea, in which a tracheomegaly with tracheomalacia was found. No signs of relapsing polychondritis were present. The respiratory symptoms rapidly improved after glucocorticoids and Azathioprine. Tracheomegaly or Mounier-Kuhn syndrome is characterized by marked dilatation of trachea and central bronchi. The differential diagnosis and the possible relationship between tracheomegaly and GCA involving metalloproteinase-induced elastolysis are discussed. This is the first case, to our knowledge, of Mounier-Kuhn syndrome in vasculitis. The association of tracheomegaly with GCA may be underestimated, as the diagnosis is not always obvious on conventional radiographs. A tracheal enlargement finding in GCA requires monitoring to ensure early detection and prevention of spontaneous tracheal rupture. Adding a metalloproteinase inhibitor like Doxycycline to GCA therapy would be rational for the prophylaxis of complications.

Ultrasonographic findings in hyperimmunoglobulin D syndrome: a case report.

Hyperimmunoglobulin D syndrome due to mevalonate kinase deficiency is a rare autoinflammatory disease with digestive tract involvement. We report an 11-year female child who has presented since the age of 1 year, bouts of fever, rash, joint swelling, pulmonary consolidation, lymph node involvement and hepatosplenomegaly. Hyperimmunglobulin D and increased urinary mevalonic acid were detected. The ultrasonographic features of hepatosplenomegaly ranged from increment in size to pseudotumoral involvement, with hypoechogenic masses without apparent wall. Abdominal CT during a disease flare showed hypodense, hypoenhancing nodular lesions, suggesting metastases. Nevertheless, a thorough search for malignancy was negative and the masses disappeared after the flare. Mevalonate kinase deficiency may add to the causes of hepatosplenic and pulmonary inflammatory pseudotumors.

Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis.

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.

Redundant plantar skin folds.

A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to lipoatrophy after recurrent episodes of plantar panniculitis. In this context, leukopenia with lymphopenia, thrombocytopenia and positive antinuclear antibodies were revelatory for systemic lupus erythematosus. However, a small cerebriform plantar collagenoma, along with discrete dysmorphic features with downslanting palpebral fissures and mild right ptosis, second and third syndactyly and a larger first right toe since childhood, and early-onset bilateral ovarian cystadenoma, suggested a minimal Proteus syndrome. Genetic confirmation could not be performed. As adipose tissue dysregulation may be a feature of Proteus syndrome, the possible mechanisms leading to localized lipoatrophy in this setting are discussed. This case enlights intriguing links between adipogenesis, inflammation and dysmorphology. From a practical point of view, finding and treating an over-imposed inflammation could help limit damage in a hamartomatous syndrome.

Mastoiditis and facial paralysis as initial manifestations of temporal bone systemic diseases - the significance of the histopathological examination.

UNLABELLED: Several systemic diseases, including granulomatous and infectious processes, tumors, bone disorders, collagen-vascular and other autoimmune diseases may involve the middle ear and temporal bone. These diseases are difficult to diagnose when symptoms mimic acute otomastoiditis. CASE REPORTS: The present report describes our experience with three such cases initially misdiagnosed. Their predominating symptoms were otological with mastoiditis, hearing loss, and subsequently facial nerve palsy. The cases were considered an emergency and the patients underwent tympanomastoidectomy, under the suspicion of otitis media with cholesteatoma, in order to remove a possible abscess and to decompress the facial nerve. The common features were the presence of severe granulation tissue filling the mastoid cavity and middle ear during surgery, without cholesteatoma. The definitive diagnoses was made by means of biopsy of the granulation tissue from the middle ear, revealing granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) in one case, middle ear tuberculosis and diffuse large B-cell lymphoma respectively. After specific associated therapy facial nerve functions improved, and atypical inflammatory states of the ear resolved. CONCLUSIONS: As a group, systemic diseases of the middle ear and temporal bone are uncommon, but aggressive lesions. After analyzing these cases and reviewing the literature, we would like to stress upon the importance of microscopic examination of the affected tissue, required for an accurate diagnosis and effective treatment.

The role of ultrasonography in assessing disease activity in patients with rheumatoid arthritis and associated fibromyalgia.

AIM: The purpose of this study is to compare and correlate US evaluation with clinical scores of the disease activity in patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (FM). MATERIAL AND METHODS: Ten patients diagnosed with RA according to the 2010 ACR/EULAR classification criteria and associated FM based on the ACR 1990 classification criteria and two control groups, one with RA (10 patients) and one with FM (10 patients), were included. Clinical assessment was performed and the disease activity scores were calculated. Synovial/tenosynovial hypertrophy, fluid collections in grey scale (GS), and Power Doppler (PD) US assessed by US in the 28 joints included in the disease activity score 28 (DAS28). RESULTS: GS US score and PD US scores were correlated with DAS28 only in patients with RA (Pearson r coefficients 0.3 and 0.5). Mean DAS28 score was significantly higher in the RA/FM group, compared to RA and FM (5.6 versus 4.6 versus 4.5, respectively). Patients with RA/FM had similar median US scores to RA patients, while in FM group significantly lower median US scores were detected (16 versus 9.5 versus 0 for GS US and 3.5 versus 1.5 versus 0 for PD US, respectively). CONCLUSIONS: Disease activity scores should be interpreted with caution in patients with RA and FM. When available, US should be used to guide treatment decisions in patients with RA and FM.

A case of alkaptonuria - ultrasonographic findings.

Alkaptonuria is a rare disease with autosomal recessive inheritance and variable expression. The weight-bearing joint involvement and spondylitis-like vertebral changes occur only after the 3rd decade. Musculoskeletal ultrasonographic findings in alkaptonuria were only rarely described, consisting mainly into enthesopathy and non-synovial tendon degeneration. We present the case of a 50 years old man with alkaptonuria and discuss the ultrasonographic findings and the relationship of the disease with chondrocalcinosis. The tendinous and synovial aspect may be peculiar and it could therefore allow recognition and screening for alkaptonuria, along with clinical and radiologic data.