Erythematous Dermatitis Research Articles

A CASE SERIES OF HLA-B*58:01 SPECIFIC ALLOPURINOL-INDUCED DRESS/DIHS

<h3>Introduction</h3> Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS) represents a severe adverse drug reaction with a high mortality rate. Allopurinol-induced DRESS/DIHS can be associated with polymorphisms in human leukocyte antigen (HLA) genes, with higher prevalence of the HLA-B*58:01 allele in Asians (7.4%) and Africans (3.8%) compared to other ethnic populations. <h3>Case Description</h3> We report four cases (two of African and two of Asian descent) of severe allopurinol-induced DRESS/DIHS requiring hospitalization for treatment. All patients presented with a generalized, erythematous dermatitis and peripheral eosinophilia after recently starting allopurinol. RegiSCAR scoring ranged from 7-8. All cases were HLA-B*58:01 positive with skin punch biopsies consistent with DRESS/DIHS. Two patients had mucocutaneous involvement, while three had notable organ involvement and relapse of disease after tapering immunosuppressant therapies. Half of the patients had evidence of viral reactivation. One patient succumbed to infectious pulmonary complications and cyclosporine toxicity. Table 1 summarizes the characteristics, laboratory findings and clinical courses of these cases. <h3>Discussion</h3> Our case series demonstrated two African and two Asian patients with severe allopurinol-induced DRESS/DIHS with positive HLA-B*58:01 genotyping. This allele has been associated with an increased risk of DRESS/DIHS from allopurinol. Detection of HLA*58:01 has higher prevalence in Asians and Africans and may portend worse disease. Recent guidelines recommend screening for the HLA*58:01 allele in Southeast Asian and African patients prior to initiation of allopurinol. Our case series highlights the importance of recognizing populations with high HLA-B*58:01 allele frequency before introduction of allopurinol to prevent DRESS/DIHS.

A sharply marginated erythematous dermatitis in a toddler.

A sharply marginated erythematous dermatitis in a toddler.

Type IV hypersensitivity to timolol

Type IV hypersensitivity to timolol

Drug-induced toxic epidermal necrolysis with secondary aspergillus fumigatus infection: a case report

Among the various drug induced dermatological entities toxic epidermalnecrolysis (TEN) and Stevens-Johnson syndrome (SJS) occupy a primary place in terms of mortality. Toxic epidermal necrolysis also known as Lyell's syndrome was first described by Lyell in 1956. Drugs are by far the most common cause of toxic epidermal necrolysis, in which large sheets of skin are lost from the body surface making redundant the barrier function of the skin, with its resultant complications. Drug-induced toxic epidermal necrolysis are severe adverse cutaneous drug reactions to various precipitating agents that predominantly involve the skin and mucous membranes. Toxic epidermal necrolysis is rare but considered medical emergencies as they are potentially fatal. Drugs are the most common cause accounting for about 65%-80% of the cases. The most common offending agents are sulfonamides, NSAIDs, butazones and hydrantoins. An immune mechanism is implicated in the pathogenesis, but its nature is still unclear. There is a prodormal phase in which there is burning sensation all over the skin and conjunctivae, along with skin tenderness, fever, malaise and arthralgias. Early sites of cutaneous involvement are the presternal region of the trunk and the face, but also the palms and soles, rapidly spread to their maximum extent, the oral mucosa and conjunctiva being affected. Initial lesions are macular, followed by desquamateion, or may be from atypical targets with purpuriccenters that coalesce, from bullae, then slough. The earlier a causative agent is withdrawn the better is the prognosis. Several treatment modalities given in addition to supportive care are reported in the literature, such as systemicsteroids, high-dose intravenous immunoglobulins, ciclosporin, TNF antagonists. Recovery is slow over a period of 14-28 days and relapses are frequent. Mortality is 25%-50% and half the deaths occur due to secondary infection. Here we report a 50-year-old female of drug-induced toxic epidermal necrolysis. She was admitted to the dermatology ward with extensive peeling of skin over the trunk and limbs. She had taken alamotrigine for epilepsy. A week after taking the tablets, the patient developed a severe burning sensation all over the body and followed by a polymorphic erythematous dermatitis and widespread peeling of skin. We treated this patient with high dose corticosteroids, high-dose intravenous immunoglobulins and etanercept, but eventually she died of secondary aspergillus fumigatus infection.

Dermatitis caused by autochthonous Cercopithifilaria bainae from a dog in Florida, USA: clinical, histological and parasitological diagnosis and treatment

Cercopithifilaria bainae is a tick-vectored filarioid nematode associated with erythematous dermatitis in dogs. It has not been reported previously in the United States. To describe clinical, histological and parasitological diagnosis and treatment of C.bainae in a dog. An 11-month-old golden retriever/standard poodle mixed breed dog from Florida (USA). The dog had no travel history within or outside the United States, was presented with a one month history of annular erythematous plaques on the head and ulcers on the medial canthi. Lesions were unresponsive to antibiotic treatment. Histopathological evaluation of skin biopsies revealed an eosinophilic to lymphohistiocytic perivascular dermatitis with multiple microgranulomas and rare 5-10μm diameter microfilariae within microgranulomas. Microfilarial morphology was consistent with C.bainae. PCR and sequencing of 18S rRNA and mitochondrial cytochrome oxidase subunit I genes confirmed the nematodes as C.bainae. The dog was treated with a commercial spot-on containing imidacloprid and moxidectin, and clinical resolution occurred. To the best of the authors' knowledge, this is the first report of C.bainae in a dog in the United States and the first description of dermatological lesions caused primarily by C.bainae.

Feline maculopapular cutaneous mastocytosis: a retrospective study of 13 cases and proposal for a new classification.

Cutaneous mastocytosis is a disorder rarely reported in veterinary dermatology and usually described as 'urticaria pigmentosa'. This study aimed to evaluate the diagnosis, treatment and outcome of 13 affected cats, selected from the files of a private referral dermatology practice within a period of 14 years. Breeds of the affected individuals included Sphynx (n = 9), Devon Rex (n = 2) and Sphynx/Devon Rex crossbreeds (n = 2). Females (n = 9) were over-represented and the median duration of clinical signs prior to diagnosis was 8 months. The clinical presentation of these 13 cats was compared with cases reported in the veterinary literature and classified according to the current human consensus on cutaneous mastocytosis. Three clinical forms could be distinguished in cats: (1) large papular lesions and wheals, typically localised to the head, shoulders, ventral neck and axillae, and which may spontaneously resolve (termed polymorphic maculopapular cutaneous mastocytosis); (2) erythematous dermatitis, characterised by small maculopapular lesions often associated with crusts and with a poorer prognosis (termed monomorphic maculopapular cutaneous mastocytosis); and (3) more chronic dermatitis characterised by lichenification and hyperpigmentation, similar to the human condition 'urticaria pigmentosa' (termed pigmented maculopapular cutaneous mastocytosis). Histopathology was performed in eight cases and revealed a superficial-to-deep dermatitis characterised by infiltrates of mast cells and eosinophils. The response to various treatments, including antihistamines, steroids and ciclosporin, was variable. This article reports 13 new cases of feline cutaneous mastocytosis, confirming the clinical presentation and apparent breed predisposition. The feline maculopapular cutaneous mastocytosis seems to be clinically very close to the human form. This study proposes a new classification system for the feline disease based on the current human consensus, clinical presentation and prognosis, with three different subforms: polymorphic maculopapular cutaneous mastocytosis with eventual spontaneous regression; monomorphic maculopapular cutaneous mastocytosis with chronic evolution; and pigmented maculopapular cutaneous mastocytosis.

A Case of Poorly Differentiated Cutaneous Canine Mast Cell Tumor with an Atypical Dermatologic Presentation

Canine cutaneous mast cell tumors occur as nodular dermal lesions. A condition of mastocytosis is also described in dogs. The purpose of this study is to report the clinical and histopathological findings in a dog with high grade non-nodular cutaneous mast cell tumor. An 11-year-old intact male German Shepherd dog presented a severe erythematous dermatitis and erythematous plaques on the left thoracic wall, rapidly increasing in thickness, ulcerating, and spreading to the head. The fine needle cytology was indicative of a round cell neoplasm. The histological appearance of the lesions was suggestive of a high grade cutaneous mast cell tumor. Neoplastic cells were immunoistochemically Tryptase positive and c-kit positive (focal cytoplasmic staining), with a high Ki67 index. On the basis of this report high grade canine cutaneous mast cell tumors may show an atypical non-nodular presentation and should be included in the differential diagnosis for different lesions grossly appearing as erythematous dermatitis/plaques.

CD45+, CD68+ and E-cadherin+ Expressions in Skin Dogs Naturally Infected by Leishmania infantum

Background: In canine leishmaniasis (CanL), infection occurs through phlebotomine vectors that inoculate the protozoan Leishmania infantum into the skin that infected macrophages and activated dendritic cells (CD). Dogs with CanL present variable clinical manifestations, being common the presence of cutaneous lesions. The aim of this study was to evaluate the expression of CD45+, CD68+ and E-cadherin+ associating the skin sentinels cells and to compare the clinical-dermatological manifestations in the skin of dogs naturally infected by L. infantum.Materials, Methods &amp; Results: Dogs infected (n = 22) by L. infantum were divided into asymptomatic group (AD, n = 9), and symptomatic group (SD, n = 13), according criteria based on the presence or absence of skin changes. Dogs non-infected (CD, n = 5) were included as control group. Samples of skin biopsies collected from scapular region were processed by routine histology and labeled by immunohistochemistry with monoclonal antibodies against CD45+, CD68+ and E-cadherin+, and were described as none, mild, moderate and intense. SD presented keratoconjunctivitis, onychogryphose, lichenification, depigmentation, alopecia, hypotrichosis, erythematous dermatitis, exfoliative dermatitis, ulcerative dermatitis and crusted dermatitis, and the frequency these alterations was expressed as percentage. The results of hematological and biochemical parameters were analyzed by Kruskal-Wallis test followed by the Dunn’s test and expressed as mean ± standard deviation, with values P &lt; 0.05. Leukocytosis (not significant), red blood cells, hematocrit and hemoglobin (P &lt; 0.05), total protein serum (P &lt; 0.05), globulins (P &lt; 0.05), albumin and A/G ratio (P &lt; 0.01) were altered in SD in relation to CD. Cutaneous cellular infiltration, composed by macrophages, plasma cells, lymphocytes and neutrophils, was observed in CD. There was an increase of expression of the markers in SD when compared to the other groups, as moderate CD68+ expression and L. infantum, and intense CD45+ and E-cadherin+ expressions.Discussion: Cutaneous involvement is very important in CanL, as it corresponds to where is the first interaction between the parasite and the immune system. Dermatological clinical signs, leukocytosis, anemia, globulins levels have been reported for dogs naturally infected by L. infantum. Inflammatory infiltrate was distributed at superficial and deep dermis, which was composed by mononuclear cells as macrophages, plasma cells, lymphocytes and neutrophils. To characterize the immune sentinels cells in the skin it was evaluated CD45+, CD68+ and E-cadherin+ expressions. In syntomatic dogs, our results revelead an increase of expression of these markers. CD45+ is one of the most abundant molecules expressed on the white blood cell surface in various mammals, while CD68+ is a myelomonocytic marker that seems to be retained during monocyte differentiation. In the skin, increased numbers of CD68+ are related to dendritic epidermal cells, which can be expressed as CD45+/CD1a-/HLA-DR+. DCs of the skin, particularly epidermal Langerhans cells (LCs), form networks anchored to neighboring keratinocytes via E-cadherin. Thus, CD45+, CD68+ and E-cadherin+ expressions may be related to activation of skin sentinels cells in dogs naturally infected by L. infantum. Our results indicated that CanL modify the CD45+, CD68+ and E-cadherin+ expressions, which characterize the immune sentinels cells activation that promove the recruitment the cellular infiltrate, which was composed by macrophages, plasma cells, lymphocytes and neutrophils. Thus, these informations may contribute to the follow-up of CanL progression in skin.

Allopurinol causing generalized exfoliative dermatitis: a case report

Erythroderma is a scaly, erythematous dermatitis of the skin, which occurs in drug allergy, malignancy and underlying skin disorders. The diagnosis is challenging because the extent of skin involvement does not always correlate with the extent of internal organ involvement. Therefore, early recognition of symptoms is vital to minimize morbidity and mortality. Case report: A 52 years old man had asymptomatic hyperuricemia and prescribed allopurinol 300mg, daily. One month later, the rashes started to appear on his trunk and then progressed to the face and upper limbs. Then it continued to spread to the lower extremities. Management involves prompt cessation of the culprit drug, administration of corticosteroids and supportive treatment. It is Concluded that Allopurinol is commonly used in clinical practice for the treatment of symptomatic hyperuricemia and gout. It has been associated with erythroderma especially when used indiscriminately.

Skin Damage and Aesthetic Disadvantage Observed in Women in the Hand Craft Shelling Chain of Cashew Nuts in a Factory to Bobo-Dioulasso, Burkina Faso

Introduction: Occupational dermatitis has long been an unforeseen consequence of industrial progress. Today, most occupational diseases are dermatosis throughout the world. The morbidity and the various prejudices concern different actors, especially those of the cashew industry in Bobo-Dioulasso to Burkina Faso. We considered it appropriate to conduct this study in women who handle cashew nuts in the cashew nut shelling station at a factory. The aim is to contribute to the search for preventive and curative solutions adapted to this health risk. Methods: This was a prospective cross-sectional study with a descriptive purpose in May 2016. The study involved 112 women present in the factory in the shelling unit and having given their approval during our visit. This station is occupied by 118 women. Results: The prevalence of all dermatosis and dermatitis was estimated respectively at 98.21% and 88.39%. The manual shelling station with a shearing machine was exclusively occupied by illiterate women (72.3%) without personal protective equipment, with an average age of 33.74 ± 8.49 years. Among the clinical forms of contact dermatitis, the erythematous contact dermatitis was most observed (86.4%), followed by palmar keratoderma (70.9%), nail disorders (33.6%) and chemical burns (30%). The implication of Cashew Nut Shell Liquid (CNSL) was established with identified promoting factors. Aesthetic damage related to hand injuries had a significant psychosocial impact in 97.32% of cases. Discussion: Few studies exist on dermatitis and the health impacts in the reality of cashew because they reach vulnerable subjects without social welfare and health protection. The cashew nuts shell contains a highly irritating brown oily liquid. Dermatitis occurs during contact with this oily juice. The international literature reports this corrosive effect throughout the history of the chain. Human factors, technical factors and work environment aggravate the situation and compromize workwomen health. Conclusion: Cashew huskers had dermatitis with an impact on daily life. Working conditions and security of employment, hygiene attitudes and anacardic acid were identified as causes of this situation. It is imperious to take measures in collaboration with the occupational physicians to ensure these women’s health at work and improve their quality of life.

Maniac psychosis and erythematous dermatitis induced by disulfiram

Maniac psychosis and erythematous dermatitis induced by disulfiram

Red face and fungi infection

Red face syndrome is characterized by an erythematous dermatitis that is produced by different entities. These include rosacea, seborrheic dermatitis, contact dermatitis, atopic dermatitis, psoriasis, cutaneous lupus, photodermatosis, post-topical steroid dermatosis, demodicosis, borderline borderline (BB) leprosy, mastocytosis, carcinoid, postneoplasia flushing, cutaneous lymphoma, tineas, ulerythema ophryogenes, and psychosomatic flushing. Red face is a relatively common dermatologic manifestation. Our goal is to review tinea corporis and other fungi that affect this region causing facial erythema and its therapeutic management.

Visual Diagnosis: 2-week-old Has a Red, Peeling Rash

1. Anita Gupta, MD* 2. Norman Jacobs, MD† 1. *Neonatology Fellow, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL. 2. †Attending Physician, John H. Stroger Jr. Hospital of Cook County, Chicago, IL. A 2-week-old term female presents to the emergency department with a history of an abrupt, generalized red rash with peeling of the skin. Her mother reports that she first noticed the skin peeling around her daughter’s umbilicus 3 days ago, about the same time the umbilical cord stump fell off. She also noted some brownish discharge from the umbilicus at that time. Twenty-four hours earlier, the infant had developed irritability and a generalized red rash over her body, with areas of peeling skin. There is no history of fever, cold, hypothermia, cough, or eye discharge. Up to this point, the infant has been feeding and stooling well. The infant was born term via a normal spontaneous vaginal delivery without complications. Birthweight was 2,700 g, and Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. However, the maternal group B Streptococcus status was unknown; the mother received two doses of intravenous penicillin 4 hours before delivery. On physical examination, the patient’s vital signs are appropriate for age, and there is no fever. The infant reacts to touch as if it hurts. Examination of the skin reveals erythroderma (scaling erythematous dermatitis) and large, thin sheets of peeling skin with underlying shallow, bright red erosions around the face (Fig 1), lower abdomen, axillae and antecubital fossae (Fig 2), and both ankles and feet (Fig 3). There are no vesicles or bullae. There is no increased erythema around, or oozing or crusting from, the periumbilical area. The mucous membranes of the mouth and anus are unaffected. The rest of the physical examination is normal for age. A clinical diagnosis is made. …

Pustulosis subcórnea (enfermedad de Sneddon-Wilkinson): Caso clínico

We report a 35-year-old female patient with a one year history of a pustular and painful erythematous dermatitis, located in great folds, pubis and abdomen. She was evaluated in primary health care, receiving antifungal treatment, antimicrobials, topical and systemic non-steroidal anti-inflammatory drugs, with no response. A skin biopsy was compatible with subcorneal pustular dermatosis. She was initially treated with prednisone (0.8 mg/kg), observing a partial response. Therefore clotrimoxazole was initiated, obtaining an excellent response after 30 days of treatment.

Erythroderma in the era of biological therapies

Erythroderma is a scaling erythematous dermatitis involving 90% or more of the cutaneous surface. Psoriasis and eczema are the most common dermatoses underlying erythroderma. Cutaneous T cell lymphomas can also cause erythroderma. Differential diagnosis between psoriatic erythroderma and lymphomatous erythroderma is often challenging. Tumour necrosis factor-alpha inhibitors are a new class of drugs used in the treatment of psoriasis, even in erythrodermic psoriasis. The effects of anti-tumour necrosis factor-alpha in cutaneous T cell lymphomas have not yet been established. Consequently, it is mandatory to treat an erythrodermic psoriatic patient with tumour necrosis factor-alpha blockers only if a lymphoproliferative cutaneous disorder has been excluded.

Tinea corporis due to Trichophyton rubrum in a Woman and Tinea capitis in her 15-Day-Old Baby: Molecular Evidence of Vertical Transmission

We report a case of a 40-year-old Caucasian woman who came under our observation with a 7-year history of a chronic erythematous scaly dermatitis, diagnosed as psoriasis, involving gluteal area and thighs, and treated with topical steroids without benefit. During pregnancy, a progressive worsening of her condition and an extension of cutaneous lesions were observed. Her newborn, a 15-day-old girl, presented a similar scaly and squamous lesion on her scalp. Mycological examination was positive for Trichophyton rubrum in both cases, and random amplified polymorphic DNA analysis confirmed the isogenicity of the two isolates. We performed a diagnosis of T. rubrum tinea corporis and tinea capitis. The case we describe illustrates an unusual clinical presentation of tinea corporis with remarkable extension of cutaneous lesions due to the diagnostic delay and the continuous use of local steroids, together with a rare tinea capitis in the newborn. Our experience highlights the possibility of mother-child transmission and the importance of an early diagnosis.

Airborne allergy to isophoronediamine and epoxy resin

Keywords:: Airborne allergic contact dermatitisbricklayerepoxy resinepoxy resin hardenerisophoronediamine

Dermatite de contato por mercúrio elementar com reação a distância

A clinical case of contact dermatitis following direct skin contact with elemental mercury is presented. Patient had metal mercury in contact with extensive part of his leg and foot skin resulting in erythematous, edematous, and vesicular dermatitis. Lesions evolved to erythematous plaques with small scattered areas of necrosis and drying vesicle lesions. Distant lesions appeared in the right forearm, chest and abdomen. Urinary mercury 36h after contact was 5.9 microg/L, and one week later 19.6 microg/L, indicating dermal absorption. dermal absorption. Dermal effects due to elemental mercury must be expected after direct skin contact.

A case of idiopathic granulomatous cheilitis and vulvitis

A 36-year-old woman presented with chronic recurring dermatitis of the vulva, perineum, and lips. The genital lesions had a 3-year history and were associated with slight pruritus and occasional pain. The lesions of the upper lip had a history of 6 months. The patient had been treated with cycles of antimycotics and topical steroids which only partially controlled the symptoms during treatment. Dermatologic examination showed erythematous, infiltrative dermatitis with edema of the labia majora and persistent edema of the upper lip (Fig. 1a,b). Routine blood chemistry, urine analysis, and chest X-ray were normal. Microscopic examination and cultures of vaginal swabs did not reveal any pathogenic bacteria or fungi. Histologic examination of a biopsy of vulval lesional skin showed lichenoid lymphocytic infiltration of the papillary dermis and small, nonnecrotic epithelioid granulomas in the deep dermis (Fig. 1c,d). No microorganisms, including acid-fast bacilli or fungi, were identified. Culture was negative for fungi. Polymerase chain reaction was negative for the mycobacterial genome. Histologic examination of a biopsy from the upper lip showed similar results. The pathology reports of both regions were compatible with a diagnosis of granulomatous cheilitis and vulvitis. To investigate concomitant asymptomatic inflammatory bowel disease, the patient underwent colonoscopy with retrograde ileoscopy and gastroscopy, which were both negative. The patient refused radiographic examination of the small intestine with a barium meal. The patient was treated with systemic metronidazole (500 mg/day). After 6 months of therapy, the upper lip showed significant improvement and erythema and desquamation in the genital area showed slight improvement, but genital edema was unaffected.

Lithium use in special populations

Byline: E. Mohandas, V. Rajmohan Lithium, a monovalent cation, was first used for the treatment of mania in the 1940s. Half a century into its use, the drug continues to be the preeminent choice for bipolar disorder with antimanic, antidepressant (modest) and antisuicidal property. Lithium is the "gold standard" mood stabilizer against which potential mood stabilizer agents are judged. The therapeutic uses of lithium also include use as an augmenting agent in depression, schizoaffective disorder, aggression, impulse control disorder, eating disorders, attention deficit disorder and in certain subsets of alcoholism. Lithium has been used in many medical disorders, especially cluster headache and dermatological disorders (seborrheic dermatitis, eczematoid dermatitis, genital herpes).[sup] [1] The drug is however associated with neurologic, endocrine, cardiovascular, renal, dermatologic and gastrointestinal adverse effects and possible teratogenicity. History Lithium was first discovered and defined by Johan August Arfvedson in 1817 when he did an analysis of the mineral petalite [LiAl(Si2O5)2]. Petalite was first found by Brazilian scientist Jose Bonifacio Andrade e Silva in 1800. Lepidolite, spodumene, petalite and amblygonite are the more important minerals containing lithium. It was Arfwedson's laboratory chief John Jacob Berzelius who named this alkali metal "lithion." Arfvedson was never able to fully isolate lithium, and it wasn't until 1855 that it was isolated by William Thomas Brande. Brande and Sir Humphrey Davy earlier had done electrolysis on lithium oxide in 1818. Lithium was first produced commercially in 1923 by Metallgesellschaft AG.[sup] [2] The use of lithium for medicinal purposes can be traced back 1,800 years to the Greek physician Galen, who treated patients with mania by having them bathe in alkaline springs and drink the water, which probably contained lithium. In 1843 Alexander Ure introduced lithium into modern medicine, and he showed the in vitro reduction of weight of a uric acid bladder stone in a lithium carbonate solution. Sir Alfred Garrod later discovered that gouty uric acid deposits also were soluble in lithium solution. The view in that time was that uric acid imbalances caused a wide range of diseases, and Armand Trousseau and Alexander Haig proposed that mania and depression also may result from this imbalance and lithium may be effective in these conditions. In the 1840s, lithium was mixed with carbonate or citrate to form a salt and was used to treat gout, epilepsy, diabetes, cancer and insomnia. In the 1870s, the then American Surgeon General William Hammond had provided anecdotal evidence for the use of lithium bromide in the treatment of acute mania. In the 1880s and 1890s the Lange brothers Carl and Fritz used lithium in depression, and Carl Lange was the first to systematically use lithium in the acute and prophylactic treatment of depression.[sup] [2] The introduction of lithium preparations and tablets in the 1900s brought to the fore the toxic effects of the drug; and there were reports of weakness, tremor, diarrhea, vomiting and deaths. The drug disappeared from the British Pharmacopoeia by 1932, but later in the 1940s it was used as a sodium substitute in low sodium diets; but the reports of severe intoxication led to its removal from American markets in 1949. [sup] [1] The appearance in 1949 in the Medical Journal of Australia of a paper entitled "Lithium salts in the treatment of psychotic excitement" by John F. J. Cade was an unspectacular entry into a new era of psychiatry. Manic patients showed improvement, with the patient becoming calmer after four to five days. There was no improvement in the excited schizophrenic patients, though there was a calming effect. There was no improvement or deepening of depression. The paper also gave details of initial dosage, maintenance doses, appearance of toxic symptoms and warning about lithium over-dosage. …