Aldo Morrone

Management of pain and fatigue in the joint hypermobility syndrome (a.k.a. Ehlers–Danlos syndrome, hypermobility type): Principles and proposal for a multidisciplinary approach

Joint hypermobility syndrome (JHS), or Ehlers–Danlos syndrome (EDS) hypermobility type (EDS‐HT), is a underdiagnosed heritable connective tissue disorder characterized by generalized joint hypermobility and a wide range of visceral, pelvic, neurologic, and cognitive dysfunctions. Deterioration of quality of life is mainly associated with pain and fatigue. Except for the recognized effectiveness of physiotherapy for some musculoskeletal features, there are no standardized guidelines for the assessment and treatment of pain and fatigue. In this work, a practical classification of pain presentations and factors contributing in generating painful sensations in JHS/EDS‐HT is proposed. Pain can be topographically classified in articular limb (acute/subacute and chronic), muscular limb (myofascial and fibromyalgia), neuropathic limb, back/neck, abdominal and pelvic pain, and headache. For selected forms of pain, specific predisposing characteristics are outlined. Fatigue appears as the result of multiple factors, including muscle weakness, respiratory insufficiency, unrefreshing sleep, dysautonomia, intestinal malabsorption, reactive depression/anxiety, and excessive use of analgesics. A set of lifestyle recommendations to instruct patients as well as specific investigations aimed at characterizing pain and fatigue are identified. Available treatment options are discussed in the set of a structured multidisciplinary approach based on reliable outcome tools.

Deploying artemether-lumefantrine with rapid testing in Ethiopian communities: impact on malaria morbidity, mortality and healthcare resources.

Objective  To assess the impact and feasibility of artemether‐lumefantrine deployment at community level, combined with phased introduction of rapid diagnostic tests (RDTs), on malaria transmission, morbidity, and mortality and health service use in a remote area of Ethiopia.

Genetic skin diseases predisposing to basal cell carcinoma

Basal cell carcinoma (BCC) is the commonest cancer in humans. Predisposing factors reflect common genetic variations and environmental influences in most cases. However, an underlying Mendelian disorder should be suspected in a specific subset of patients, namely those with multiple, early onset lesions. Some specific conditions, including Gorlin, Bazex-Dupré-Christol and Rombo syndromes, and Xeroderma Pigmentosum, show BCC as a prominent feature. In addition, BCC may represent a relatively common, although less specific, finding in many other genodermatoses. These include disorders of DNA replication/repair functions (Bloom, Werner, Rothmund-Thomson and Muir-Torre syndromes), genodermatoses affecting the folliculo-sebaceus unit (Brooke-Spiegler, Schöpf-Schulz-Passarge and Cowden syndromes), immune response (cartilage-hair hypoplasia and epidermodysplasia verruciformis) and melanin biosynthesis (oculocutaneous albinism and Hermansky-Pudlak syndrome), and some epidermal nevus syndromes. Further conditions occasionally associated with BCCs exist, but the significance of the association remains to be proven.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM To evaluate if indolent B cell-non Hodgkins lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%). CONCLUSION HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.

Gynecologic and obstetric implications of the joint hypermobility syndrome (a.k.a. Ehlers–Danlos syndrome hypermobility type) in 82 Italian patients†‡

Joint hypermobility syndrome (JHS) emerges as likely the most common clinical form of Ehlers–Danlos syndrome. Given the striking predominance of affected women, practitioners often face gynecologic and obstetric issues. However, their decisions are still based on personal experience rather than literature due to the lack of a consistent body of evidence. We collected a set of gynecologic and obstetric features in 82 post‐puberal women with JHS attending two Italian centers. Common gynecologic findings were dysmenorrhea (82.9%), meno/metrorrhagias (53.7%), irregular menses (46.3%), and dispareunia/vulvodinia (31.7%). Forty women were nulliparous and 42 had one or more pregnancy for a total of 93 diagnosed conceptions. Of them, 16.1% were spontaneous abortions, 6.5% voluntary interruptions, 10.7% preterm deliveries, and 66.7% deliveries at term. Overall outcome of proceeding pregnancies was good with no stillbirth and fetal/neonatal hypoxic/ischemic event. Non‐operative vaginal delivery was registered in 72.2%, forceps/vacuum use in 5.5% and cesarean in 22.3%. Local/total anesthesia was successfully performed in 17 pregnancies without any problem. Major post‐partum complications included abnormal scar formation after cesarean or episiotomy (46.1%), hemorrhage (19.4%), pelvic prolapses (15.3%), deep venous thrombosis (4.2%), and coccyx dislocation (1.4%). Prolapses were the most clinically relevant complication and associated with episiotomy. Gathered data were discussed for practically oriented considerations.

Cutaneous and mucocutaneous leishmaniasis in Tigray, northern Ethiopia: clinical aspects and therapeutic concerns

Leishmaniasis is a worldwide disease, but due to the absence of surveillance systems is under-reported from low- and middle-income countries. In Ethiopia, the disease is found in the rural highlands and the incidence of Leishmania/HIV co-infection is increasing. Although some studies have been carried out in areas of the country with a similar disease/ecological profile this report is, to our knowledge, the first aimed at elucidating the clinical-epidemiological features of cutaneous and mucocutaneous leishmaniasis in Tigray, northern Ethiopia. This study enrolled 167 patients presenting different forms of cutaneous leishmaniasis over an 18 month period, of which 5.6% tested HIV positive. Patients were initially treated with meglumine antimonate and resistant cases with pentamidine isethionate. There was a high rate of resistance to meglumine antimonate (28%) and a less than optimal response to prolonged systemic treatment in relapsed cases. Eight patients affected by severe and resistant forms were treated with pentamidine isethionate, with a cure rate of 87.5% after 6 months. Many atypical and severe presentations were seen, and a poor response to first-line antileishmanial drugs was observed. Resistance to antimonials is of concern and cost-effective therapeutic schemes need to be developed. The cost-effectiveness of pentamidine isethionate has to be determined in a larger population.

Treatment of hepatitis C virus carriers with persistently normal alanine aminotransferase levels with peginterferon α-2a and ribavirin: a multicentric study

Background/Aims: To evaluate, in clinical practice, the efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV) carriers with normal alanine aminotransferase (ALT) levels.

Clinical and Epidemiological Study of Cutaneous Tuberculosis in Northern Ethiopia

Background: Tuberculosis is a major public health problem in Ethiopia but cutaneous tuberculosis (CT) has not been documented. Objective: This study was conducted to determine its existence and its clinical pattern in Tigray, a northern region of Ethiopia. Methods: We report 202 cases of CT who attended the Italian Dermatological Centre in the 34-month period between January 2005 and October 2007. The diagnosis was made on a clinical, cytological and histological basis. Results: Clinically, 143 cases of scrofuloderma, 22 of lupus vulgaris, 18 of gumma, 11 of lichen scrofulosorum, 6 of tuberculosis verrucosa cutis and 2 of erythema induratum of Bazin were observed in our department. All patients were aged between 18 months and 69 years, and 49 were paediatric cases. Forty-five were HIV positive. Conclusion: The number of CT cases observed in the period of 34 months indicates a high incidence of the disease in the region also in the paediatric age. CT is still underdiagnosed due to the low number of dermatologists as well as the poor life conditions of the population and the traditional belief in magic medicine. The current study may therefore provide some indication about the epidemiology of CT in Ethiopia.

Poverty, health and development in dermatology

The WHO Constitution states that “The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being without distinction of race, religion, political, economic or social condition.”

TFR2-related hereditary hemochromatosis as a frequent cause of primary iron overload in patients from Central-Southern Italy

OBJECTIVE Hereditary hemochromatosis (HH) is a common Mendelian disorder of iron metabolism. Eighty percent of northern Europeans descendant HH patients carry the same mutation (p.C282Y) in the HFE gene. Simultaneously, due to a founder effect, its frequency varies considerably between different populations. In Central-Southern Italy the prevalence of p.C282Y mutation is low and in several patients the disease has different causes. Four additional rarer forms have been described. Type 3 HH has been reported in about 50 families and no more than 30 TFR2 pathogenic mutations have been globally identified. The aim of this study is to assess the TFR2 role in non-HFE HH pathogenesis. STUDY DESIGN AND SETTING TFR2 sequence analysis was performed on 45 Italian patients without HFE mutations. RESULTS This study revealed TFR2 biallelic pathogenic mutations in 7/45 (15.6%) individuals. Moreover monoallelic TFR2 deleterious defects (18%) or polymorphisms with unclear meaning (36%) were identified. Besides, we recognized 10 novel variants and 9 described changes. CONCLUSION We believe this to be the largest series of type 3 HH patients described so far. Present findings support the hypothesis of a main role of the TFR2 gene in HH pathogenesis in those regions, such as Central-Southern Italy, where the p.C282Y frequency is low.