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Aetiology Caused by infection by the commensal yeast Pityrospo- Erythematous lesions rumorbiculare (also known as Malessezia furfur cheap proventil 100mcg overnight delivery, Pity- rosporum ovale and Malassezia ovalis) cheap proventil 100 mcg visa. Infection results Erythema multiforme from conversion of the yeast to the mycelial or hyphal form buy proventil 100mcg with amex, which may be triggered by heat and humidity and Denition immunosuppression. Theyeastreleasescarboxylicacids, Aself-limiting hypersensitivity reaction affecting the which inhibit melanin production. Aetio- F > M logical agents include: r Herpes simplex in 33% of cases; may cause recurrent Aetiology attacks. Clinical features r Gastrointestinal disorders: Inammatory bowel dis- Lesions are pinkish red erythematous papules/plaques ease, Behcet s syndrome and bacterial gastroenteri- with central clearing or concentric rings (target lesions). Disseminated rash with mucosal Clinical features involvement with conjunctivitis and necrotic mucosal Painfulbluish-rednodulesupto5cmindiameterappear ulcers is termed Stevens Johnson syndrome. This is of- in crops over 2 weeks on the anterior surface of both ten associated with systemic symptoms. The withdrawal of any causative drug and treatment of any associated infection is essential. Short courses of Management oral steroids are sometimes used but their efcacy and Symptomatic treatment and management of any under- safetyareunclear. Recovery may take weeks, and tiforme resulting from herpes simplex can be prevented there may be recurrence. Urticaria Prognosis Disease is usually self-limiting clearing in 2 3 weeks but Denition death can occur with Stevens Johnson syndrome. Urticaria is an itchy erythematous eruption ranging from nettle rash to large weals/plaques with palpable skin oedema. Most cases of urticaria are acute and self- Erythema nodosum limiting within a few hours, occasionally with recurrent episodes for up to 6 weeks. Chronic urticaria lasts from 6 weeks Erythema nodosum is an immune-mediated disorder and up to 10 years. There is often no identiable trigger resulting in red tender pretibial subcutaneous nodules. Any trigger factor should be identied and avoided IgE mediated Food allergy (egg, milk, wherever possible. Medical treatment is used for symp- peanut) Drug reaction (penicillin, tomrelief in acute urticaria and chronic urticaria where cephalosporin) triggers are not identiable. Insect stings (bees, wasps) 1 Antihistamines Contact allergy (latex) r H receptor blockers such as loratadine are the 1 Complement mediated Hereditary angio-oedema mainstay of treatment. Serum sickness r H receptor blockers such as ranitidine may be use- Transfusion reactions 2 Direct mast cell Opiates (morphine, codeine) ful in conjunction with an H1 blocker in refractory degranulation Neuromuscular blocking cases. Prolonged courses in Vancomycin Radiological contrast agents chronic urticaria are associated with signicant side Infections Coxsackie A and B effects and adrenal suppression. Uncommon in very Rarely urticaria may bepart of a systemic disease, such as young and very old. Sex M = F Pathophysiology Aetiology/pathophysiology Urticaria results from the degranulation of cutaneous The exact cause is unknown but it is thought that there mast cells causing dilation of local capillaries and leakage is a T cell autoimmune reaction to keratinocytes. There is a lichen planus like eruption, associated with Clinical features many drugs (see Table 9. Trauma may play a role as lesions occur at sites of skin trauma (Koebner phenomenon). Patients often describe severe pru- ritus, and healing results in hyperpigmentation. Clinical features Hypertrophic lichen planus is a variant with hyper- Lichen sclerosis is most commonly seen in the anogeni- keratotic plaques seen on the legs. Patients may complain of itching, dysuria and r Lichen planus of the scalp is termed lichen planopi- dyspareunia. On examination there are atrophic, white laris, which can cause a scarring alopecia. Extragenital white plaques due to striae in the mouth, or plaques or erosive ulceration. An erosive lichen planus affecting the orogenital regions is seen in Complications women termed vulvovaginal-gingival syndrome. Management High potency topical steroids are the mainstay of treat- Investigations ment. Refractory cases may respond to systemic steroids, Abiopsy may be required if the diagnosis is not clear. A lymphocytic inltrate is seen in the lower Prognosis dermis, and immunouorescence may be required to Mostlesionsclearwithin2yearsleavinghyperpigmented exclude cicatricial pemphigoid. Hypertrophic, anogenital and mucosal involve- ment is more persistent and more refractory to treat- Management ment. Surgery is avoided due to the Koebner phe- Denition nomenon but may be required for adhesions, phymosis Lichen sclerosus (previously lichen sclerosus et atroph- or introital stenosis. Long-term follow-up with biopsy icus) is an uncommon chronic progressive disorder of of any area suspicious of squamous cell carcinoma is the skin characterised by inammation and epithelial recommended.

Neuropathic pain may develop also after peripheral nerve trauma as in the condition of chemotherapy-induced neuropathy generic 100mcg proventil with mastercard. The frequencies of many types of peripheral neuropathic pain are not known in detail but vary considerably because of differences in the frequency of underlying diseases in different parts of the world order 100mcg proventil with mastercard. While pain caused by leprosy is common in Brazil and parts of Asia order proventil 100mcg online, such pains are exceedingly rare in Western parts of the world. Because of an explosion in the frequency of diabetes as a result of obesity in many industrialized countries and in South-East Asia, the likely result of this will be an increase in painful diabetic neuropathy within the next decade. Central neuropathic pain, including pain associated with diseases of the spinal cord. Central post-stroke pain is the most frequently studied central neuropathic pain condition. Two thirds of patients with multiple sclerosis have chronic pain, half of which is central neuropathic pain (3). Damage to tissues of the spinal cord and, at times, nerve roots, carries an even higher risk of leading to central neuropathic pain (myelopathic pain). The cause may lie within the cord and be intrinsic, or alternatively, be extrinsic outside the cord. Intrinsic causes include multiple scle- rosis and acute transverse myelitis, both of which may result in paraplegia and pain. In certain developing countries, for example in sub-Saharan Africa, intrinsic damage may be attributable to neurotoxins as in the case of incorrectly prepared cassava, which leads to tropical spastic neurological disorders: a public health approach 129 paresis. Other causes include compressive lesions, for example tumours and infections, especially tuberculosis and brucellosis. Pain indirectly caused by diseases or abnormalities of the nervous system Pain arises as a result of several distinct abnormalities of the musculoskeletal system, secondary to neurological disorders. These can be grouped into the following categories: musculoskeletal pain resulting from spasticity of muscles; musculoskeletal pain caused by muscle rigidity; joint deformities and other abnormalities secondary to altered musculoskeletal function and their effects on peripheral nerves. Pain caused by spasticity Pain caused by spasticity is characterized by phasic increases in muscle tone with an easy pre- disposition to contractures and disuse atrophy if unrelieved or improperly managed. In developed countries, the main causes of painful spasticity are strokes, demyelinating diseases such as multiple sclerosis, and spinal cord injuries. Strokes and spinal cord disease are also major causes of spasticity in developing countries, for example stroke is the most common cause of neurological admissions in Nigeria. Pain caused by muscle rigidity Pain can be one of the rst manifestations of rigidity and is typically seen in Parkinson s disease, dystonia and tetanus. Apart from muscle pain in the early stages of Parkinson s disease, it may also occur after a long period of treatment and the use of high doses of L-Dopa causing painful dystonia and freezing episodes. Tetanus infection, common in developing countries, is characterized by intense and painful muscle spasms and the development of generalized muscle rigidity, which is extremely painful. During intense spasm, fractures of spinal vertebrae may occur, adding further pain. Pain caused by joint deformities A range of neurological disorders give rise to abnormal stresses on joints and, at times, cause deformity, subluxation or even dislocation. For example frozen shoulder or pericapsulitis occurs in 5 8% of stroke patients. Disuse results in the atrophy of muscles around joints and various abnormalities giving rise to pain, the source of which are the tissues lining the joint. In addition, deformities may result in damage to nerves in close proximity resulting in neuropathic pain of the evoked or spontaneous type. The literature does not give data for the prevalence and incidence of the pain associated with the disorders mentioned. The symptoms exceed both in magnitude and duration those which might be expected clinically given the nature of the causative event. Other features of the syndrome include local oedema or swelling of tissues, abnormalities of local blood ow, sweating (autonomic changes) and local trophic changes. They are a cause of signicant psychological and psychiatric disturbance, and treatment is a major problem. They have been the subject of considerable research and been carefully classied by the International Headache Society. Epidemiological studies have focused primarily on migraine and tension-type headaches (primary headache disorders). Pain is a subjective experience but physiological changes that accompany it may be measured: they include changes in heart rate, muscle tension, skin conductivity and electrical and metabolic activity in the brain. These measures are most consistent in acute rather than chronic pain and they are used primarily in laboratory studies. The use of words as descriptors of pain have permitted the development of graded descriptions of pain severity. Such measures are often repeated at intervals to gain information about the levels of pain throughout the day, after a given procedure or as a consequence of treatment. More sophisticated verbal measures use groups of words to describe the three dimensions of pain, namely its sensory component, the mood-related dimension and its evaluative aspect. This technique was devised by Melzack and others and is best seen in the Short-Form McGill Pain Questionnaire (5).

Bayer makes a general commitment arate ad hoc donations for disaster relief and to build manufacturing capacity in countries in public health emergencies discount proventil 100mcg fast delivery, including following Adaptations of brochures and packaging to scope generic 100 mcg proventil with mastercard. The company undertakes a small number the 2016 Nepal earthquake and 2014-2015 Ebola address range of needs discount 100 mcg proventil mastercard. Bayer facilitates the of capacity building activities in a range of rel- epidemic. These activities focus on the and by using blister packs to improve product industry standards for Good Manufacturing stability in hot and humid conditions. Bayer s approach to health-related phil- anthropic projects is relatively weak: it includes Laggard in Patents & Licensing. Bayer drops 10 impact measurement but does not target local positions in this area, to 18th place. It does not Innovation: open-source pharmacovigi- publish the status of its patents in countries in lance tool. It has an internal policy not to fle for pat- Interest Group within the International Society ents in Least Developed Countries. The group brings together Southeast Asian regulatory authorities Does not engage in licensing and makes no and international experts to develop and share public commitment to doing so in future. Bayer innovative risk-minimisation methods and tools, does not engage in licensing, nor does it publicly including an open-source tool for developing acknowledge the potential usefulness of licens- customised risk-management guidelines. Bayer breaches, fnes or judgements relating to com- is engaged in long-term donation programmes petition law during the period of analysis. Although it is a leader does have an access-to-medicine strategy, but it is not clearly in Patents & Licensing and has improved moderately in aligned with corporate strategy. The company consistently other areas, this is outweighed by signifcant falls in Market engages in licensing, now also for hepatitis C products. The company was found equitable pricing strategies for the same number of products to have engaged in corrupt practice in China. Despite a strong approach to philanthropy, it lags a small pipeline of relevant products and a conservative in capacity building, particularly in the areas of pharmacovigi- approach to sharing clinical trial data. Bristol-Myers Squibb can expand strengthen supply chain management and phar- sider expanding its access-oriented product the range of factors (beyond environmental macovigilance systems. For example, it can systematically take explore similar approaches for its ischaemic account of local languages, literacy levels, cul- heart disease and stroke products. Bristol-Myers Squibb can Expand strategic capacity building activities clearly link its R&D strategy to high-burden dis- to support local access to medicine. Bristol- eases and access needs in low- and middle-in- Myers Squibb has a strong approach to philan- come countries. The company can also develop thropic capacity building in health-related areas, plans to ensure new products are accessible in beyond the production and supply of medi- these markets soon after they leave the pipeline. Bristol-Myers Other revenues include: royalties and alliance-related revenues Squibb has sales in 37 countries within the scope for products not sold by regional commercial organisations. It is adapting products for diseases in scope, but did tor for diarrhoeal diseases and two medicines for ischaemic heart disease. Rises two positions with a clearer access Below average in governance of ethical mar- Bristol-Myers Squibb does not clearly commit strategy. Bristol-Myers Squibb contractually to sharing its clinical trial results within a speci- places from 17th. It has provided a clearer def- enforces the application of its marketing code to fed timeframe. The company has a mechanism nition of its access strategy and improved in third parties. Nevertheless, it only uses sales tar- for third parties to request patient-level data: an the way it measures performance. It does not internal committee approves requests before transparency of its stakeholder engagement publish information about marketing activities in they are sent to an independent review commit- activities is low. Bristol-Myers Collaborates through intellectual property Squibb s access-to-medicine strategy focuses Squibb discloses its policy positions related sharing. It only dis- Pasteur Korea and the University of Dundee (6) Improving Health Care Infrastructure and closes some of the fnancial contributions it with access to its compound libraries. Its aim is Practices; (7) Patents, Licensing and Technology makes to the trade associations it has joined. Audits are conducted once every Has access initiatives, but no explicit align- two to three years. Bristol-Myers Squibb access-to-medicine strategy aligns with its cor- remains in 12th position.