David A. Sacks MD

  • Adjunct Investigator
  • Department of Research
  • Southern California Permanente Medical Group
  • Pasadena, California
  • Clinical Professor
  • Department of Obstetrics and Gynecology
  • Keck School of Medicine
  • University of Southern Califor

Investigations There are no consistent laboratory abnormalities in acne fulminans muscle relaxant easy on stomach trusted imitrex 25 mg. There is one report describing a patient with acne fulminans and a lytic bone lesion from which P muscle relaxant juice generic imitrex 25 mg with mastercard. This contrasts with another report in which a patient had osteomyelitis and acne fulminans but cultures from bone were negative for P muscle relaxant shot for back pain cheap imitrex online amex. Characteristically spasms calf purchase 50 mg imitrex fast delivery, a leucocytosis is found sometimes with an associated leukaemoid reaction muscle relaxant 771 cheap 25 mg imitrex mastercard. Elevated liver enzymes and microscopic haematuria muscle relaxant review buy generic imitrex 100mg, proteinuria and other kidney abnormalities may be identified. Differential diagnosis the main differential diagnosis is severe acne conglobata (see later). Bone involvement is common and approximately 50% of patients have lytic bone lesions demonstrated by radiographs and 70% show increased uptake using technetium scintigraphy. Destructive lesions resembling osteomyelitis are demonstrated on radiographs in 25% of patient [658]. When present, bone biopsies have been performed to rule out malignancy; the histology usually reveals reactive changes only but a neutrophilic infiltrate with mononuclear cells and granulation tissue can mimic osteomyelitis. Patients with osteolytic lesions may have elevated serum alkaline phosphatase [659]. Oral isotretinoin should be used with caution as paradoxically it has been reported to induce acne fulminans in some patients [664]. Complications Radiographic changes such as hyperostosis and sclerosis may persist but rarely the symptoms and signs associated with any bony changes typically resolve with treatment. Mild musculoskeletal discomfort has been reported as a persistent symptom following the acute episode. Alternative therapies Clofazimine 200 mg three times a week has been shown to improve acne fulminans [665]. Pulsed intravenous corticosteroids administered alongside isotretinoin have been used to control the disease in a 16yearold male with good effect [666]. Isotretinoin in combination with dapsone has been used successfully to treat acne fulminans associated with erythema nodosum [664]. In cases of acne fulminans which appear in the context of autoinflammatory disease, the effective use of biologicals has been described in some cases but others have noted improvement in the musculoskeletal symptoms without much impact or in some cases a deterioration in the cutaneous problems. Disease course and prognosis the prognosis for patients treated effectively with corticosteroids and isotretinoin is extremely good. Relapse may occur as corticosteroid therapy is reduced but the risk reduces over time and is unusual after a year. The acute myalgia, arthralgia and fever can be treated with oral salicylates or nonsteroidal antiinflammatory drugs and graduTable 90. Multiple polyporous, grouped comedones are typical and extensive disfiguring hypertrophic and atrophic scars are also common features [675]. Introduction and general description Acne congolobata has a chronic and persistent course, it may occur in the context of existing papulopustular acne or may present as a recrudescence of acne that has been in abeyance for many years. Lesions typically occur on the trunk and upper limbs but frequently extend to the buttocks. The malodorous, discharging sinus tracts and significant scarring frequently result in psychological impairment. Predisposing factors Acne conglobata, like acne fulminans, can be triggered by testosterone and may be induced by anabolic steroid abuse and can occasionally occur after withdrawal of testosterone [687]. Acne conglobata may also occur in the context of an androgensecreting tumour and has been described following exposure to aromatic hydrocarbons or ingestion of halogens (see Occupational acne). Causative organisms No causative organisms have been implicated in the pathophysiology of acne conglobata. Mycobacterium chelonae I infection has been described as a mimic of acne conglobata in an immunocompetent host [687]. Ethnicity There are no studies to indicate that acne conglobata is seen more frequently in different ethnic groups. Associated diseases Acne conglobata may occur in the context of a number of inflammatory disorders. The association of acne conglobata and arthritis is rare but has been reported in a number of case reports [678,679,680]. Acne conglobata has been described in association with pyoderma gangrenosum [682]. A number of autoinflammatory syndromes cite acne conglobata as a possible clinical presentation within the context of the syndrome; these are described in more detail in Chapter 49. The healing of lesions is slow and associated with significant discomfort and disfiguring scarring. Patients present with acne conglobata at an older average age and the condition has a protracted and more chronic course than acne fulminans with fewer systemic symptoms (see section on Acne fulminans; see Table 90. Comedonal lesions are generally much more florid in acne conglobata and present in a characteristic grouped manner. Severe acne vulgaris, occupational acne and drug induced acne should be considered in the differential diagnosis. Resultant scarring may be improved with the fractional laser postsurgical intervention [696]. Second line Tetracycline antibiotics are frequently prescribed to reduce the inflammation but are notoriously ineffective. Classification of severity Acne conglobata always presents as a severe cutaneous inflammatory process with significant scarring resulting in disfigurement in most cases. Psychosocial sequelae as a result of the disease process and resultant scarring are very common [691]. Alternative therapies Alternative options for the management of acne conglobata include longterm highdose antibiotics, dapsone with isotretinoin [701], ciclosporin and/or colchicine in conjunction with topical retinoids and antimicrobial therapy [698]. One case report has demonstrated the benefit of carbon dioxide laser in combination with tretinoin to open up cysts and to prevent the emergence of new lesions [696]. There are very few clinical trials assessing treatment in this refractory condition but one small study examining photodynamic therapy using 5% aminolaevulinic acid and red light demonstrated some advantage to control therapy [707]. Potential treatments for acne conglobata as reported in the literature are outlined in Table 90. It leads to significant psychosocial morbidity as a result of extensive scarring and discomfort and malodour associated with the inflammatory lesions. Assessment No consistent laboratory abnormalities are identified in acne conglobata. Bacterial cultures from the skin are generally sterile but in some cases lesions are secondarily infected with Grampositive bacteria. In cases where there is malodour, assessing cultures and treating with appropriate antibiotics may be helpful. An IgA gammopathy has been observed in a patient with pyoderma and acne conglobate [692]. Histologically, they consist of elaborate, epithelialized galleries connected to the skin surface at multiple points. The draining sinus contains corneocytes, hairs, bacteria, serum, inflammatory cells and epithelioid granulomas [713]. Treatment should aim to reduce the morbidity associated with discomfort and malodour with the use of appropriate analgesia alongside antiseptic washes and if necessary antibiotics. Treatment should also aim to prevent complications by reducing inflammation associated with resultant scarring. Large nodules may be aspirated and injection with intralesional triamcinolone or cryotherapy may be beneficial [694]. More extensive surgical excision of interconnecting nodules and laying open of sinus tracts my also prove helpful [695]. There are reports of benefit with laser therapy and modern external beam radiation [696,697]. A combination of medical and surgical approaches may be required to manage this refractory condition [698]. Recent reports have also indicated that some of the novel biologicals may be helpful in this challenging condition. Occupational acne Definition and nomenclature Occupational acne is a group of disorders characterized by the formation of acnelike lesions in previously acne nonprone patients after exposure to occupational agents, in most cases chemical compounds. Isotretinoin may need to be combined with oral antibiotics such as erythromycin or trimethoprim. With or without systemic steroids 1 patient 64yearold male Etanercept Infliximab 3 mg/kg. Etanercept then tapered to once a week for 1 month then alternate weeks for 2 months and isotretinoin reduced to 10 mg daily Marked decrease in size and degree of inflammation of nodular lesions by 4 weeks at 12 weeks full resolution of nodular lesions. At 12 months on treatment sustained efficacy Reduction in lesions and activity of the disease Duration/outcome of treatment Reduction in some inflammatory lesions and better control of disease but not clearance in many Successful treatment Reduction of lesions at week 6 No new lesions after week 6 Isotretinoin tapered off Control maintained with infliximab Successful treatment of acne with infliximab Clinical improvement with laser, maintained with tretinoin Successful treatment achieved 3 weeks postradiation reduced cyst size, absent drainage, reduced pain and improved selfesteem All dermatologocal and rheumatological manifestations reported to regress with infliximab. Chloracne is caused by certain polyhalogenated organic (aromatic) compounds containing naphthalenes, biphenyls and phenols (herbicides and herbicide intermediates) and is considered to be one of the most sensitive indicators of systemic poisoning by these compounds [718] (Box 90. Aetiology Acne venenata/acne cosmetic Tropical acne/ hydration acne Oil acne/pomade acne Detergens acne Cosmetics Heat/humidity Oil Location Face Back, neck, buttocks, proximal extremities Arms, thighs, buttocks Hands, face Lesions Closed comedones Nodules, cysts Erythematous papules, pustules Erythematous papules, pustules Open comedones Comedones, straw coloured cysts (0. Dioxins, a large family of halogenated aromatic hydrocarbons, are the most potent environmental chloracnegen. The chloracnegens are structurally similar, containing two benzene rings with halogen atoms occupying at least three of the lateral ring positions (75 isomers). Associated diseases Due to its extensive longterm developmental and neurological toxicity, hormonal and immunological disruption as well as cancer promotion, the production of polychlorinated biphenyls has been prohibited by the Stockholm Treaty on Persistent Organic Pollutants made effective from 2004. Epidemiology Most cases of chloracne have resulted from occupational and nonoccupational exposures. Nonoccupational chloracne mainly resulted from contaminated industrial wastes and contaminated food products. The identification of dioxin as an elicitor of occupational acne was made with the cooperation of the dermatologists K. Sorge in Hamburg, Germany, who investigated patients with atypical acne in a chemical plant [720]. Since then, there have been several large accidents caused by occupational exposures or food contaminations. A history of exposure to chloracnegens, progressively emerging comedones, papules, nodules and cysts followed by scars, skin xerosis and decreased sebogenesis, and high serum concentration of chloracnegens (Table 90. Clinical signs Usual age Comedones Inflammatory papules and cysts Strawcoloured cysts Temporal comedones Retroauricular involvement Nose involvement Associated systemic findings Chloracne Any Many (essential sign) Uncommon Pathognomonic Diagnostic Common Often spared Common Acne vulgaris Adolescent Present Common Rare Rare Uncommon Involved Rare 90. Management the aim of treatment is to lower or to eliminate the accumulated dioxins in the body at the very beginning of intoxication, The problem of dioxin contamination and its potential health hazards should be taken seriously during the current wave of industrial globalization. A broad range of treatment options are available but some medications used in the management of adult acne are contraindicated in children [729]. Epidemiology Incidence Neonatal acne defined as the presence of even a small number of comedones may affect up to 20% of neonates; however, this may reflect an overestimate as papulopustular conditions may masquerade as neonatal acne [730]. Infantile acne is less common than neonatal acne and midchildhood acne is very rare [732,733]. Descriptive terms used for acne in preadolescent children are generally based on age and include neonatal, infantile, midchildhood and prepubertal or preadolescent acne. A recent classification of acne in children based on expert consensus included five subtypes according to age, i. However, the distinction between preadolescence and adolescence by age can be challenging; the term prepubertal acne has been adopted for use in this text. Infantile acne typically presents between 3 and 12 months but may occur as late as 16 months [738]. Introduction and general description Prepubertal acne includes a number of clinical presentations and may be misdiagnosed. The definition by age does not necessarily identify children that are at risk of treatable forms of virilization and a focused history and examination should be adopted to ensure underlying hormonal abnormalities, adrenal or gonadal tumours are identified. Adrenarche represents maturation of the adrenal glands with adrenal production and increase in the return of the zona reticularis and acquisition of enzymes that facilitate synthesis of androgens from cholesterol. There appears to be a reduction of peripheral androgen production in these patients and the use of conventional hormonal replacement therapy that further decreases testosterone and dihydrotestosterone may explain the absence of moderate to severe acne in Turner syndrome. Pathophysiology the underlying pathogenesis of neonatal acne is not clearly understood but thought to relate to hyperactivity of the sebaceous glands stimulated by neonatal androgens from the testes in boys and adrenals in girls and boys [742].

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Topical nicotinamide Topical nicotinamide 4% has antiinflammatory actions and does not induce P muscle relaxant neck pain cheap imitrex 100 mg online. A comparison of 4% nicotinamide gel demonstrated it to be similar in efficiency to 1% clindamycin gel [588] quinine muscle relaxant mechanism discount 100mg imitrex amex. Corticosteroids A few topical preparations contain weak corticosteroids but proof of their efficacy is lacking muscle relaxant vs pain killer cheap imitrex express. Potent steroids such as clobetasol propionate applied twice a day for 5 days can dramatically reduce the inflammation in an active inflammatory nodule [594] spasms meaning in urdu cheap imitrex online mastercard. A further review examined the empirical evidence for the efficacy of complementary therapies in acne and concluded that many of the therapies were biologically plausible but in general poor methodology had been used in the studies spasms left abdomen buy imitrex with paypal. The authors concluded that further rigorously conducted trials were required to define efficacy and adverse effect profiles of currently used complementary therapies for acne [597] spasms lower left side purchase 25 mg imitrex amex. Further validation for safety and efficacy against standard medicines is required. The cautery or hyfrecation should be set as low as possible to produce little or no pain. Blue light reduced inflammatory lesions compared to the control and was superior to no treatment in reducing acne [602,603]. Blue light has been given a low strength recommendation in the management of mild to moderate papulopustular acne. Lasers and photodynamic therapy There has been increased interest in the use of lasers and lightbased devices for acne over the last few years. Light therapy destroys propionibacteria by targeting porphyrins produced by these bacteria. Many of the studies include small numbers, short followup periods and have adopted nonstandardized regimes. They have also not compared these therapies to conventional treatments used for acne. Outcome measures have also been very variable, making comparison between trials and metaanalysis difficult. No robust studies are available to support the use of lasers or photodynamic therapy for comedonal acne. However, the confidence intervals for the results were large reflecting the small numbers of subjects and no definite conclusions could be drawn from this. Light therapy may cause pain, erythema, crusting, oedema, pigmentary changes and pustular eruptions. The intensity of these problems is more likely when aminolaevulinic acid or methyl aminolevulinate are employed in the treatment, and frequently leads to the patient not pursuing further therapy. The other concern relates to longterm safety, as sebocytes are necessary for the immune function of the skin and may be permanently damaged by photodynamic therapy. Patients should be informed of the existing evidence, which indicates that optical treatments are not currently included among first line treatments for acne but remain of interest and under investigation. It most frequently affects the trunk but can affect the face and presents acutely in association with systemic symptoms. The disease was later distinguished from acne conglobata by Plewig and Kligman in 1975 [617] they emphasized the characteristic features of sudden onset and severity of systemic upset as distinct features. It is a rare form of acne and the incidence appears to be diminishing, possibly due to more effective and earlier use of treatments [618]. Peeling agents include hydroxy acids (glycolic acid), salicylic acid and trichloroacetic acid. Guidelines and evidence for their use have been considered in a Japanese review [614]. A recent review of the efficacy of a variety of chemical peels for acne showed an average reduction in comedones by 35%; however, published studies are limited by sample size and design [615]. Evidence for the use of chemical peels in the treatment of acne is therefore lacking but they are relatively safe and inexpensive and many dermatologists worldwide use light chemical peels with the aim of helping to remove comedones as well as superficial scarring and hyperpigmentation. Epidemiology Age and gender Acne fulminans is predominantly seen in young white males aged between 13 and 22 years [620] although there have been rare cases reported in females [621]. Ethnicity the frequency and severity of acne fulminans is notably greater in patients of Northern European descent compared with those from EastAsian origin [622,623]. Acne fulminans has also been reported at the onset of Crohn disease but the significance of this association remains unclear [624]. There is just one case report of acne fulminans and ulcerative colitis in a 19yearold Japanese male patient suggesting any association is very rare [625]. Infection, genetic predisposition and immunological causes have all been suggested. One theory suggests acne fulminans is an autoimmune complex disease, in favour of this is the rapid response to systemic steroids, increased levels of globulins and decrease in complement levels seen in a number of patients. Immune complexes are found predominantly in patients with musculoskeletal problems. Another theory is that genetically determined changes in neutrophil activity/hyperreactivity to chemoattractants may result in reduced phagocytosis of P. It has been suggested that patients who develop very severe flares of acne after starting isotretinoin may have an exaggeration of this response [640]. Genetics Hereditary factors may play a role, acne fulminans has been reported in identical monozygotic twins who presented at the same age with identical clinical presentation [641,642]. A genetically determined change in neutrophil activity has also been proposed as a determinant. Predisposing factors Acne fulminans is seen most frequently in young males and there is some evidence to suggest that elevated blood levels of testosterone may play a role [628]. The increase in physiological levels of testosterone in males at puberty may explain this predisposition. One case of acne fulminans has also been reported in a young man with androgen excess as a result of lateonset congenital adrenal hyperplasia [633]. As derivatives of the hormone testosterone, anabolic steroids lead to hypertrophy of the sebaceous glands, increased sebum production and as a result of this an increased density of P. In some patients, mild cystic acne rapidly evolves with ulcerative and necrotic lesions. Environmental factors Infection as a trigger for acne fulminans has been reported. One case report indicates an association 2 weeks after a measles infection implying that the virus may trigger a transient release of inflammatory cytokines, resulting in acne fulminans in a predisposed individual [644]. Clinical features History Most patient with acne fulminans describe mild to moderate acne for 0. These are predominantly distributed on the upper chest, back and shoulders [646] and pyogenic granulomatouslike lesions may be present. The face may also be involved and the lesions undergo rapid degeneration resulting in ulcerations filled with necrotic debris. Systemic signs and symptoms are present in the majority of patients and include malaise, arthralgia, joint swellings, polyarthritis, myalgia, fever, and anorexia and weight loss. A marked leucocytosis which may be leukaemoid is frequent; patients may also demonstrate anaemia (Table 90. Painful splenomegaly [647], erythema nodosum [648,649] and bone pain due to aseptic osteolysis have also been reported [650]. Bone involvement is common [651]; in a series of 24 patients, 48% had lytic bone lesions on Xray and 67% showed increased Pathology Causative organisms the presence in some patients of microscopic haematuria, erythema nodosum, increased response to P. Hypotheses to explain this suggest that the isotretinoin induced fragility of the pilosebaceous duct epithelium allows significant exposure of P. Patients present with acne conglobata at an older average age and the condition has a protracted and more chronic course than acne fulminans with little or much less systemic symptoms. The sites of predilection for bone lesions include the anterior chest, particularly the clavicles and sternum, but osteolytic lesions have also been reported in the ankles, hips and humerus. Assessment Acne fulminans always presents as a severe cutaneous inflammatory process with varying systemic signs and symptoms. During the neonatal period and for approximately 1 year afterwards, the adrenals secrete androgens. This restarts in midchildhood, around 7 years of age, at which time the zona reticularis produces androgens again. Increased sebum production in the first few months returns to normal at about 6 months. Similar to neonatal acne, it may be associated with increased levels of androgens produced by adrenal glands in both sexes and by the testes in boys. Ethnicity There are no good studies comparing ethnicity in prepubertal acne but slight variation in the onset of puberty may influence the age of onset. Associated diseases Prepubertal acne may be associated with underlying endocrinopathies and virilizing tumours. Environmental factors Certain medications may be implicated in prepubertal acne as identified in the section on druginduced acne. Exposure to certain substances including greasy emollients, hair gels, occlusive topical agents as well as aromatic hydrocarbons and halogenides may be a trigger. Clinical features In the neonatal period, acne may present at birth or shortly afterwards up to 28 days [753]. It is a selflimiting benign process and does not generally result in any scarring. Infantile acne is said to be seen more rarely than neonatal acne but is often misdiagnosed [754]. Neonatal acne typically presents after 6 months and most cases resolve by the age of 5 years but occasionally some remain as a continuum until puberty [743]. A history of a sibling with infantile acne may be notable and a family history of severe acne is not uncommon [755]. Production of androgens from the neonatal adrenal glands ceases around 1 year of life until the onset of adrenarche around the age of 7 years. As outlined previously, causes of hyperandrogenism should be ruled out if acne presents in this age group. The development of midfacial comedonal acne is considered a predictor acne severity [745]. Acute onset, persistent or severe acne particularly in the presence of virilization between 1 and 7 years of age should always raise the possibility of an underlying endocrinopathy. Infantile acne has been reported as an initial sign of an adrenocortical tumour in a 23monthold boy with accelerated growth and signs of virilization [746]. In boys, recalcitrant or severe acne may be a presenting sign of nonclassical congenital adrenal hyperplasia [748]. A focused history and examination for signs of accelerated growth, precocious puberty and hirsutism or other signs of hyperandrogenism should be employed. The central cheeks are frequently affected [754] with a combination of inflamed papules and pustules with open Predisposing factors See main section on acne vulgaris. Causative organisms Propionibacterium acnes is implicated in the pathophysiology of acne (see section on the pathophysiology of acne vulgaris). In the case of neonatal cephalic pustulosis, a relationship has been suggested between the clinical presentation and Malasezzia furfur, Malasezzia sympodialis and other species [750] but not others [751]. A study of 29 patients with infantile/juvenile acne seen in a specialist centre over a period of 25 years [755] demonstrated the median age of onset was 9 months; the disease was mild in 24%, moderate in 62% and severe in 14%. Acne developing at an early age should always raise the suspicion of androgen excess. Acne in prepubertal children usually presents with comedonal lesions with or without some inflammatory papules. Lesions are frequently located in a midfacial distribution and may precede any other signs of maturation [756]. Clinical variants Neonatal cephalic pustulosis has been considered by some as synonymous with neonatal acne but others consider it a separate entity as there are more inflammatory papules, significant pustules and a lack of comedonal lesions. Acne conglobata is a severe variant of acne that can present in infants resulting in severe inflammatory cystic lesions, sinus tract formation and significant scarring [729]. Neonatal cephalic pustulosis was first described in 1991 [759] and historically referred to as neonatal acne [731]. It is characterized by erythematous papular/pustular lesions especially on the cheeks but also on the chin, eyelids, neck and upper chest. It has been postulated that neonatal cephalic pustulosis develops in association with Malassezia sympodialis and Malassezia globosa; however, the exact aetiological role of Malassezia is uncertain, as the organism is part of the normal flora of neonatal skin, and up to 38% of cases had negative smears in one study [760]. Another explanation is that neonatal cephalic pustulosis relates to an overgrowth of lipophilic yeasts at birth that results in an inflammatory reaction leading to monomorphic papules and pustules in predisposed neonates with more sebum production.

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