Pieranna Fietta

Central nervous system effects of natural and synthetic glucocorticoids.

Natural glucocorticoids (NGC) physiologically modulate body homeostasis and coordinate adaptive responses to stress, involving almost all organs and tissues, including brain. Since their therapeutic availability, synthetic GC (SGC) have been successfully prescribed for a variety of diseases. Mounting evidence, however, demonstrated pleiotropic adverse effects (AE), including central nervous system (CNS) disturbances, which are often misdiagnosed or underestimated. The aim of the present study was therefore to review and discuss the CNS effects of both NGC and SGC. A detailed search was carried out of the available literature using the PubMed (US National Library of Medicine) database. Cortisolemia plays a crucial role in control of behavior, cognition, mood, and early life programming of stress reactivity. Hypercortisolemia or SGC treatments may induce behavioral, psychic and cognitive disturbances, due to functional and, over time, structural alterations in specific brain target areas. These AE are generally dose and time dependent (infrequent at prednisone‐equivalent doses <20 mg/day) and usually reversible. Pediatric patients are particularly susceptible. Behavioral changes, including feeding and sleeping modifications, are common. Psychic AE are unpredictable and heterogeneous, usually mild/moderate, severe in 5–10% of cases. Manic symptoms have been mostly associated with short SGC courses, and depressive disorder with long‐term treatments. Suicidality has been reported. Cognitive AE peculiarly affect declarative memory performance. Physiologic levels of NGC are essential for efficient brain functions. Otherwise, hypercortisolemia and SGC treatments may cause dose‐/time‐dependent neuropsychic AE and, over time, structural alterations in brain target areas. Clinicians should carefully monitor patients, especially children and/or when administering high doses SGC.

OPG/RANKL system imbalance in a case of hepatitis C-associated osteosclerosis: the pathogenetic key?

Hepatitis C-associated osteosclerosis (HCAO) is an impressive example of acquired diffuse osteosclerosis in adults, recently described in ten patients infected with hepatitis C virus (HCV). Its hallmark is a painful and generalized increase of bone mass. Bone biopsies show enhanced accretion rate, usually without histological abnormalities. The HCAO pathogenesis is hitherto unknown. HCV might induce a slow bone cell infection and the production of bone growth factors, such as insulin-like growth factors. Recently, receptor activator of nuclear factor-κB (RANK), its ligand (RANKL), and soluble decoy receptor osteoprotegerin (OPG) have been identified as a pivotal cytokine system in the bone remodeling control. We describe the 11th case of HCAO. Notably, the patient’s bone biopsy showed the presence of a high number of OPG-positive osteoblasts, a slight increase of RANKL-positive stromal cells, and a dramatic reduction of the osteoclasts. Moreover, OPG serum levels were increased. These findings reported here for the first time are consistent with a pathogenetic role of the OPG/RANKL system imbalance in HCAO.

Remitting Seronegative Symmetrical Synovitis with Pitting Oedema in a Patient with Myelodysplastic Syndrome and Relapsing Polychondritis

Abstract: Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) may be the inaugural manifestation of different rheumatic diseases of the elderly, malignancies and myelodysplastic syndromes (MDS). Relapsing polychondritis (RP) is a rare systemic disorder characterised by an inflammatory process involving predominantly cartilaginous structures, the cardiovascular system and organs of special sense. We report on a 72-year-old man with RS3PE and MDS, refractory anaemia subtype, diagnosed at the same time as RS3PE. Several months later the patient presented a clinical and pathological picture compatible with RP. Although the association between RP and MDS is well known, no previous cases of RS3PE preceding RP have been reported. This case confirms that RS3PE may herald many diseases, among others autoimmune disorders such as RP.

Clinical and histological coexistence of inflammatory pseudotumour of the lymph nodes and rheumatoid arthritis

Inflammatory pseudotumour (IPT) of the lymph nodes is an uncommon, self-limiting, non-neoplastic proliferation of spindle cells, associated with a polymorphous inflammatory cell infiltrate embedded in a collagen-rich stroma and a variable degree of fibrosis, arising in the nodal parenchyma. Its clinical picture is characterised by site-specific signs and the presence, in most cases, of constitutional symptoms. The pathogenesis of IPT is unknown, but it has been interpreted as an aberrant reactive condition of the nodal connective framework, possibly related to viral infections or chronic inflammatory conditions. Its prognosis is usually favourable. We here report the simultaneous onset of seronegative rheumatoid arthritis (RA) and nodal IPT in a 31-year-old woman. Notably, in the nodal biopsy the coexistence of rheumatoid nodules, as well as histological and immunohistochemical features of IPT, was observed. To our knowledge, such an association has not been previously reported and the hypothesis that IPT could represent an unusual epiphenomenon of an RA-related chronic inflammatory response is suggested.

Counterbalance between leptin and cortisol may be associated with fibromyalgia

We read with interest the article by Liao et al., suggesting that the counterbalance between leptin and cortisol may be associated with comorbid depression and anxiety. Leptin, the product of the obese gene mainly secreted by adipocytes, controls energy balance and exerts pleiotropic actions, integrating metabolic, immune, neuroendocrine and behavioral responses. Leptin may provide negative feedback inhibition to the hypothalamus–pituitary–adrenal (HPA) axis, which is crucial for adapting to chronic stress, and psychopathology would be the result if such a mechanism of counterbalance was impaired. Liao et al. proposed leptin as valid neuroendocrinologic marker for the hypervigilant state. Fibromyalgia (FM) is a common clinical condition defined as persistent, widespread musculoskeletal pain, in the presence of tender points at specific anatomical sites. Fibromyalgia is more than just a pain syndrome; it includes a protean series of disturbances, mainly involving autonomic, neuroendocrine and neuropsychic systems. The primary disorder seems to affect the nociceptor system, inducing aberrant amplification of pain perception, leading FM to be defined as ‘hypervigilance syndrome’. The troubling experience of a chronic psychophysical suffering state, that compels FM patients to confront an everyday ‘invisible disability’, may induce dysfunction of neuroendocrine, autonomic and psychocognitive systems of chronic stress coping. Compared with healthy controls, FM patients have a significantly higher prevalence of psychiatric disorders (PD), and such an FM/PD comorbidity may suggest a common physiopathology. Leptin–HPA axis interactions in FM were not assessed by previous studies, to our knowledge. We evaluated morning serum leptin and cortisol levels in 30 middle-aged, non-obese, untreated FM patients (10 male, and 20 postmenopausal female) with normal eating behavior, compared with age-, sexand body mass index-matched controls. Patients with PD comorbidity were excluded. We found significantly higher leptin levels in FM patients than in controls. Serum cortisol was slightly but not significantly reduced in the FM group. Further investigations on leptin–HPA axis interactions in FM are needed, as is the evaluation of circadian pattern and pulsatility, but our preliminary data suggest a leptin role in FM pathogenesis, underlining the FM essence of a generalized hypervigilant state. We agree with Liao et al. that leptin–cortisol interaction studies may contribute to the comprehension of psychopathologic mechanisms underlying PD and their comorbidity, and we suggest that they might also provide a better understanding of FM physiopathology.

Carnitine: a therapeutic option for childhood psoriatic onycho-pachydermo-periostitis (POPP).

Psoriatic onycho-pachydermo-periostitis (POPP) is a rare subset of psoriatic arthritis, characterized by onychopathy, painful thickening of the periungual soft tissues, and radiological features consisting of an exuberant periosteal reaction of the terminal phalanx. The POPP treatment is debated, and side effect risk of therapies may not be offset by their benefits. We report on a successful treatment with carnitine in a 15-year old boy suffering from POPP.

Steroid-reversible parkinsonism as presentation of polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is an inflammatory disorder typically affecting elderly people, characterized by pain and stiffness in the neck and in the shoulder and pelvic girdless with prompt clinical response to low doses of corticosteroids. PMR is closely related to giant cell arteritis (GCA), likely sustained by a “subclinical vasculitis”. Whereas in GCA both the central and peripheral nervous systems may be involved, only a PMR case of global, steroid-reversible dementia has been hitherto described. We report two elderly patients who abruptly developed, as PMR presenting symptom, an akinetic-rigid parkinsonian syndrome that promptly and completely resolved after corticosteroid treatment.