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Antibiotic ointment is typically applied to the newborn's eyes within 1 hour of birth as prevention against gonococcal ophthalmia. This maybe erythromycin, tetracycline, or silver nitrate.
Treatment is based on the prescription and use of the proper antibiotics depending on the strain of the ureaplasma.
Because of its multi-causative nature, initial treatment strategies involve using a broad range antibiotic that is effective against chlamydia (such as doxycycline). It is imperative that both the patient and any sexual contacts be treated. Women infected with the organisms that cause NGU may develop pelvic inflammatory disease. If symptoms persist, follow-up with a urologist may be necessary to identify the cause.
According to a study, tinidazole used with doxycycline or azithromycin may cure NGU better than when doxycycline or azithromycin is used alone.
If left untreated, complications include epididymitis and infertility. Consistent and correct use of latex condoms during sexual activity greatly reduces the likelihood of infection.
Prophylaxis needs antenatal, natal, and post-natal care.
- Antenatal measures include thorough care of mother and treatment of genital infections when suspected.
- Natal measures are of utmost importance as mostly infection occurs during childbirth. Deliveries should be conducted under hygienic conditions taking all aseptic measures. The newborn baby's closed lids should be thoroughly cleansed and dried.
- If it is determined that the cause is due to a blocked tear duct, a gentle palpation between the eye and the nasal cavity may be used to clear the tear duct. If the tear duct is not cleared by the time the newborn is one year old, surgery may be required.
- Postnatal measures include:
- Chemical ophthalmia neonatorum is a self-limiting condition and does not require any treatment.
- Gonococcal ophthalmia neonatorum needs prompt treatment to prevent complications. Topical therapy should include
Systemic therapy: Newborns with gonococcal ophthalmia neonatorum should be treated for seven days with one of the following regimens ceftriaxone, cefotaxime, ciprofloxacin, crystalline benzyl penicillin
- Other bacterial ophthalmia neonatorum should be treated by broad spectrum antibiotics drops and ointment for two weeks.
- Neonatal inclusion conjunctivitis caused by Chlamydia trachomatis responds well to topical tetracycline 1% or erythromycin 0.5% eye ointment QID for three weeks. However systemic erythromycin should also be given since the presence of chlamydia agents in conjunctiva implies colonization of upper respiratory tract as well. Both parents should also be treated with systemic erythromycin.
- Herpes simplex conjunctivitis should be treated with intravenous acyclovir for a minimum of 14 days to prevent systemic infection.
A variety of drugs may be prescribed based on the cause of the patient's urethritis. Some examples of medications based on causes include: azithromycin, doxycycline, erythromycin, levofloxacin, metronidazole, ofloxacin, or tinidazole.
Proper perineal hygiene should be stressed. This includes avoiding use of vaginal deodorant sprays and proper wiping after urination and bowel movements. Intercourse should be avoided until symptoms subside.
Nongonococcal urethritis (NGU) is an inflammation of the urethra that is not caused by gonorrheal infection.
For treatment purposes, doctors usually classify infectious urethritis in two categories: gonococcal urethritis, caused by gonorrhea, and nongonococcal urethritis (NGU).
The disease is classified as either gonococcal urethritis, caused by "Neisseria gonorrhoeae", or non-gonococcal urethritis (NGU), most commonly caused by "Chlamydia trachomatis". NGU, sometimes called nonspecific urethritis (NSU), has both infectious and noninfectious causes.
Urethritis is part of triad of Reiter's Syndrome.
Other causes include:
- Adenoviridae
- Uropathogenic "Escherichia coli" (UPEC)
- Herpes simplex
- Cytomegalovirus
- "Mycoplasma genitalium"
- Reactive arthritis
- "Trichomonas vaginalis"
- "Ureaplasma urealyticum"
- "Methicillin-resistant Staphylococcus aureus"
- "Group B streptococcus"
Antibiotic therapy has to overcome the blood/prostate barrier that prevents many antibiotics from reaching levels that are higher than minimum inhibitory concentration. A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium. Treatment requires prolonged courses (4–8 weeks) of antibiotics that penetrate the prostate well. The fluoroquinolones, tetracyclines and macrolides have the best penetration. There have been contradictory findings regarding the penetrability of nitrofurantoin , quinolones (ciprofloxacin, levofloxacin), sulfas (Bactrim, Septra), doxycycline and macrolides (erythromycin, clarithromycin). This is particularly true for gram-positive infections.
In a review of multiple studies, Levofloxacin (Levaquin) was found to reach prostatic fluid concentrations 5.5 times higher than Ciprofloxacin, indicating a greater ability to penetrate the prostate.
Persistent infections may be helped in 80% of patients by the use of alpha blockers (tamsulosin (Flomax), alfuzosin), or long term low dose antibiotic therapy. Recurrent infections may be caused by inefficient urination (benign prostatic hypertrophy, neurogenic bladder), prostatic stones or a structural abnormality that acts as a reservoir for infection.
In theory, the ability of some strains of bacteria to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis.
Escherichia coli extract and cranberry have a potentially preventive effect on the development of chronic bacterial prostatitis, while combining antibiotics with saw palmetto, lactobacillus sporogens and arbutin may lead to better treatment outcomes.
Bacteriophages hold promise as another potential treatment for chronic bacterial prostatatis.
The addition of prostate massage to courses of antibiotics was previously proposed as being beneficial and prostate massage may mechanically break up the biofilm and enhance the drainage of the prostate gland. However, in more recent trials, this was not shown to improve outcome compared to antibiotics alone.
Over time, the relapse rate is high, exceeding 50%. However, recent research indicates that combination therapies offer a better prognosis than antibiotics alone.
A 2007 study showed that repeated combination pharmacological therapy with antibacterial agents (ciprofloxacin/azithromycin), alpha-blockers (alfuzosin) and Serenoa repens extracts may eradicate infection in 83.9% of patients with clinical remission extending throughout a follow-up period of 30 months for 94% of these patients.
A 2014 study of 210 patients randomized into two treatment groups found that recurrence occurred within 2 months in 27.6% of the group using antibiotics alone (prulifloxacin 600 mg), but in only 7.8% of the group taking prulifloxacin in combination with Serenoa repens extract, Lactobacillus Sporogens and Arbutin.
Primary gonococcal dermatitis is a rare infection of the skin that occurs after primary inoculation of the skin from an infected focus.
Regular testing for sexually transmitted infections is encouraged for prevention. The risk of contracting pelvic inflammatory disease can be reduced by the following:
- Using barrier methods such as condoms; see human sexual behavior for other listings.
- Seeking medical attention if you are experiencing symptoms of PID.
- Using hormonal combined contraceptive pills also helps in reducing the chances of PID by thickening the cervical mucosal plug & hence preventing the ascent of causative organisms from the lower genital tract.
- Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.
- Getting a STI history from your current partner and strongly encouraging they be tested and treated before intercourse.
- Diligence in avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.
- Reducing the number of sexual partners.
- Sexual monogamy.
- Abstinence
Treatment is often started without confirmation of infection because of the serious complications that may result from delayed treatment. Treatment depends on the infectious agent and generally involves the use of antibiotic therapy. If there is no improvement within two to three days, the patient is typically advised to seek further medical attention. Hospitalization sometimes becomes necessary if there are other complications. Treating sexual partners for possible STIs can help in treatment and prevention.
For women with PID of mild to moderate severity, parenteral and oral therapies appear to be effective. It does not matter to their short- or long-term outcome whether antibiotics are administered to them as inpatients or outpatients. Typical regimens include cefoxitin or cefotetan plus doxycycline, and clindamycin plus gentamicin. An alternative parenteral regimen is ampicillin/sulbactam plus doxycycline. Erythromycin-based medications can also be used. Another alternative is to use a parenteral regimen with ceftriaxone or cefoxitin plus doxycycline. Clinical experience guides decisions regarding transition from parenteral to oral therapy, which usually can be initiated within 24–48 hours of clinical improvement.
The main infectious agents are Enterobacteriaceae (such as Escherichia coli and Klebsiella), Neisseria gonorrhoeae and Chlamydia trachomatis.
One study has shown that men with MAGI who have lower serum levels of total testosterone tend to have a more complicated form of MAGI, such as involving more than one site, than those with normal levels.
Gonococcemia (also known as "Arthritis–dermatosis syndrome" and "Disseminated gonococcal infection") is a condition characterized by a hemorrhagic vesiculopustular eruption, bouts of fever, and arthralgia or actual arthritis of one or several joints.
It's characterized by a triad of symptoms: migratory polyarthritis, tenosynovitis, and dermatitis (pustular skin lesions).
Aseptic meningitis, or sterile meningitis, is a condition in which the layers lining the brain, the meninges, become inflamed and a pyogenic bacterial source is not to blame. Meningitis is diagnosed on a history of characteristic symptoms and certain examination findings (e.g., Kernig's sign). Investigations should show an increase in the number of leukocytes present in the cerebrospinal fluid (CSF) obtained via lumbar puncture (normally being fewer than five visible leukocytes per microscopic high-power field).
The term "aseptic" is frequently a misnomer, implying a lack of infection. On the contrary, many cases of aseptic meningitis represent infection with viruses or mycobacteria that cannot be detected with routine methods. While the advent of polymerase chain reaction has increased the ability of clinicians to detect viruses such as enterovirus, cytomegalovirus, and herpes virus in the CSF, many viruses can still escape detection. Additionally, mycobacteria frequently require special stains and culture methods that make their detection difficult. When CSF findings are consistent with meningitis, and microbiologic testing is unrevealing, clinicians typically assign the diagnosis of aseptic meningitis—making it a relative diagnosis of exclusion.
Aseptic meningitis can result from non-infectious causes as well. it can be a relatively infrequent side effect of medications, or be a result of an autoimmune disease. There is no formal classification system of aseptic meningitis except to state the underlying cause, if known. The absence of bacteria found in the spinal fluid upon spinal tap, either through microscopic examination or by culture, usually differentiates aseptic meningitis from its pyogenic counterpart.
"Aseptic meningitis", like non-gonococcal urethritis, non-Hodgkin lymphoma and atypical pneumonia, merely states what the condition is not, rather than what it is. Terms such as viral meningitis, bacterial meningitis, fungal meningitis, neoplastic meningitis and drug-induced aseptic meningitis can provide more information about the condition, and without using one of these more specific terms, it is difficult to describe treatment options or prognosis.
Potential complications include:
- obstruction of the epididymis
- impairment of spermatogenesis
- impairmentment of sperm function
- induction of sperm auto-antibodies
- dysfunctions of the male accessory glands
These complications can result in
sexual dysfunction and male subfertility.
The mortality of the disease in 1909, as recorded in the British Army and Navy stationed in Malta, was 2%. The most frequent cause of death was endocarditis. Recent advances in antibiotics and surgery have been successful in preventing death due to endocarditis. Prevention of human brucellosis can be achieved by eradication of the disease in animals by vaccination and other veterinary control methods such as testing herds/flocks and slaughtering animals when infection is present. Currently, no effective vaccine is available for humans. Boiling milk before consumption, or before using it to produce other dairy products, is protective against transmission via ingestion. Changing traditional food habits of eating raw meat, liver, or bone marrow is necessary, but difficult to implement. Patients who have had brucellosis should probably be excluded indefinitely from donating blood or organs. Exposure of diagnostic laboratory personnel to "Brucella" organisms remains a problem in both endemic settings and when brucellosis is unknowingly imported by a patient. After appropriate risk assessment, staff with significant exposure should be offered postexposure prophylaxis and followed up serologically for six months. Recently published experience confirms that prolonged and frequent serological follow-up consumes significant resources without yielding much information, and is burdensome for the affected staff, who often fail to comply. The side effects of the usual recommended regimen of rifampicin and doxycycline for three weeks also reduce treatment adherence. As no evidence shows treatment with two drugs is superior to monotherapy, British guidelines now recommend doxycycline alone for three weeks and a less onerous follow-up protocol.
The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G, the original penicillin found in 1928), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V). Procaine penicillin and benzathine penicillin have the same antibacterial activity as benzylpenicillin but act for a longer period of time. Phenoxymethylpenicillin is less active against gram-negative bacteria than benzylpenicillin. Benzylpenicillin, procaine penicillin and benzathine penicillin can be given by intravenous or intramuscular injections, but phenoxymethylpenicillin can be given by mouth because of its acidic stability.
While the number of penicillin-resistant bacteria is increasing, penicillin can still be used to treat a wide range of infections caused by certain susceptible bacteria, including Streptococci, Staphylococci, Clostridium, and Listeria genera. The following list illustrates minimum inhibitory concentration susceptibility data for a few medically significant bacteria:
- "Listeria monocytogenes": from less than or equal to 0.06 μg/ml to 0.25 μg/ml
- "Neisseria meningitidis": from less than or equal to 0.03 μg/ml to 0.5 μg/ml
- "Staphylococcus aureus": from less than or equal to 0.015 μg/ml to more than 32 μg/ml
Antibiotics such as tetracyclines, rifampin, and the aminoglycosides streptomycin and gentamicin are effective against "Brucella" bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells.
Surveillance using serological tests, as well as tests on milk like the milk ring test, can be used for screening and play an important role in campaigns to eliminate the disease. Also, individual animal testing both for trade and for disease-control purposes is practiced. In endemic areas, vaccination is often used to reduce the incidence of infection. An animal vaccine is available that uses modified live bacteria. The World Organisation for Animal Health "Manual of Diagnostic Test and Vaccines for Terrestrial Animals" provides detailed guidance on the production of vaccines. As the disease is closer to being eliminated, a test and stamping out program is required to completely eliminate it.
The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for seven days is an acceptable substitute when streptomycin is not available or contraindicated. Another widely used regimen is doxycycline plus rifampin twice daily for at least six weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampin and co-trimoxazole, has been used successfully to treat neurobrucellosis.
Doxycycline is able to cross the blood–brain barrier, but requires the addition of two other drugs to prevent relapse. Ciprofloxacin and co-trimoxazole therapy is associated with an unacceptably high rate of relapse. In brucellic endocarditis, surgery is required for an optimal outcome. Even with optimal antibrucellic therapy, relapses still occur in 5 to 10% of patients with Malta fever.
The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products, or by pasteurizing all milk that is to be ingested by human beings, either in its unaltered form or as a derivate, such as cheese.
Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square meters, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.
The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.
The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.
The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.
Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data.
Treatment is usually with intravenous antibiotics, analgesia and washout and/or aspiration of the joint. Draining the pus from the joint is important and can be done either by needle (arthrocentesis) or opening the joint surgically (arthrotomy).
Empiric antibiotics for suspected bacteria should be started. This should be based on gram stain of the synovial fluid as well as other clinical findings. General guidelines are as follows:
- Gram positive cocci - vancomycin
- Gram negative cocci - Ceftriaxone
- Gram negative bacilli - Ceftrioxone, cefotaxime, or ceftazidime
- Gram stain negative and immunocompetent - vancomycin
- Gram stain negative and immunocompromised - vancomycin + third generation cephalosphorin
- IV drug use (possible pseudomonas aeruginosa) - ceftazidime +/- an aminoglycoside
Once cultures are available, antibiotics can be changed to target the specific organism.
After a good response to intravenous antibiotics, patients can be switched to oral antibiotics. The duration of oral antibiotics varies, but is generally for 1-4 weeks depending on the offending organism.
In infection of a prosthetic joint, a biofilm is often created on the surface of the prosthesis which is resistant to antibiotics. Surgical debridement is usually indicated in these cases. A replacement prosthesis is usually not inserted at the time of removal to allow antibiotics to clear infection of the region. Patients that cannot have surgery may try long-term antibiotic therapy in order to suppress the infection.
Close follow up with physical exam & labs must be done to make sure patient is no longer feverish, pain has resolved, has improved range of motion, and lab values are normalized.
Risk of permanent impairment of the joint varies greatly. This usually depends on how quickly treatment is started after symptoms occur as longer lasting infections cause more destruction to the joint. The involved organism, age, preexisting arthritis, and other comorbidities can also increase this risk. Gonococcal arthritis generally does not cause long term impairment.
Mortality rates generally range from 10-20%. These rates increase depending on the offending organism, older age, and comorbidities such as rheumatoid arthritis
Due to the high number of hosts, eradication of tungiasis is not feasible, at least not easily so. Public health and prevention strategies should then be done with elimination as the target. Better household hygiene, including having a cemented rather than a sand floor, and washing it often, would lower the rates of tungiasis significantly.
Though vaccines would be useful, due to the ectoparasitic nature of chigoe flea, they are neither a feasible nor an effective tool against tungiasis. Nevertheless, due to the high incidence of secondary infection, those at risk of tungiasis should get vaccinated against tetanus. A better approach is to use repellents that specifically target the chigoe flea. One very successful repellent is called Zanzarin, a derivative of coconut oil, jojoba oil, and aloe vera. In a recent study involving two cohorts, the infestation rates dropped 92% on average for the first one and 90% for the other. Likewise, the intensity of the cohorts dropped by 86% and 87% respectively. The non-toxic nature of Zanzarin, combined with its "remarkable regression of the clinical pathology" make this a tenable public health tool against tungiasis.
The use of pesticide, like DDT, has also led to elimination of the "Tunga penetrans", but this control/prevention strategy should be utilized very carefully, if at all, because of the possible side effects such pesticides can have on the greater biosphere. In the 1950s, there was a worldwide effort to eradicate malaria. As part of that effort, Mexico launched the Campaña Nacional para la Erradicación de Paludismo, or the National Campaign for the Eradication of Malaria. By spraying DDT in homes, the Anopheles a genus of mosquitoes known to carry the deadly Plasmodium falciparum was mostly eliminated. As a consequence of this national campaign, other arthropods were either eliminated or significantly reduced in number, including the reduviid bug responsible for Chagas disease (American Trypanosomiasis) and "T. penetrans". Controlled, in-home spraying of DDT is effective as it gives the home immunity against arthropods while not contaminating the local water supplies and doing as much ecological damage as was once the case when DDT was first introduced.
While other species gradually gained resistance to DDT and other insecticides that were used, "T. penetrans did" not; as a result, the incidence of tungiasis in Mexico is very low when compared to the rest of Latin America, especially Brazil, where rates in poor areas have been known to be as high or higher than 50%. There was a 40-year period with no tungiasis cases in Mexico. It was not until August 1989 that three Mexican patients presented with the disease. Though there were other cases of tungiasis reported thereafter, all were acquired in Africa.
As the disease is self-limiting, at least when exposure to the parasite is limited, management is mostly confined to treatment. Due to the secondary infection that can cause serious medical issues, the recommended course of action upon diagnosis is a surgical extraction of the fleas followed by the application of a topical antibiotic. Care should be taken to avoid tearing the flea during the extraction procedures as severe inflammation will result. The same will occur if part of the flea is left behind. Sterile equipment should always be used, as contaminated instruments could act as mechanical vectors for pathogens to enter the body.
There is no drug that has proven to be effective against embedded fleas. Oral niridazole was once considered a therapeutic drug, but well-designed studies are lacking and, given the severe adverse effects, this is one drug that is likely to cause more harm than good. However, it has some anecdotal evidence of lysing the fleas altogether. Oral ivermectin is considered by some in endemic areas to be a panacea against the fleas but studies using high doses have failed to validate this hypothesis. Other drugs such as topical ivermectin and metrifonate have been somewhat successful, but not enough to be significant. [2,5] For superinfections, trimethoprim, sulfamethoxazole, metronidazole, amoxicillin, (with/without clavulanate) have been used successfully, though these treat only secondary infections.
Successful topical treatments also include cryotherapy and electrodesiccation of the lesion. If formaldehyde, chloroform, or DDT are used topically, care should be taken when dealing with the resulting morbidity. The "T. penetrans" flea can also be suffocated using occlusive petrolatum, while Vaseline will kill the organism as well, most likely due to suffocation as the stigmatas would be covered. The gum of the mammee apple ("Mammea americana"), a fruit that also goes by the name Saint Domingo apricot, has also been used to kill the chigoe flea, though this has not been reported in the main "T. penetrans" literature.
Even without treatment, the burrowed fleas will die within five weeks and are naturally sloughed off as the skin sheds.
Following a successful induction of remission, maintenance therapy might be given in some cases, for example when there is a high risk of relapse or in patients with organ-threatening manifestations. Common maintenancy therapy is prednisolone 2.5–5 mg per day, or use of a steroid-sparing agent instead.