Acute generalized exanthematous pustulosis associated with clindamycin in a patient with Hailey-Hailey disease.

A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.

Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management.

PURPOSE OF STUDY: Immune-mediated adverse drug reactions occur commonly in clinical practice and include mild, self-limited cutaneous eruptions, IgE-mediated hypersensitivity, and severe cutaneous adverse drug reactions (SCAR). SCARs represent an uncommon but potentially life-threatening form of delayed T cell-mediated reaction. The spectrum of illness ranges from acute generalized exanthematous pustulosis (AGEP) to drug reaction with eosinophilia with systemic symptoms (DRESS), to the most severe form of illness, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). RECENT FINDINGS: There is emerging literature on the efficacy of cyclosporine in decreasing mortality in SJS/TEN. The purpose of our review is to discuss the typical presentations of these conditions, with a special focus on identifying the culprit medication. We review risk factors for developing SCAR, including HLA alleles strongly associated with drug hypersensitivity. We conclude by discussing current strategies for the management of these conditions.

Acute generalized exanthematous pustulosis secondary to dose-related turmeric supplementation.

We present the case of a 55-year-old woman with a 10-day history of a rapidly progressing generalized rash. History was significant for recent increase in turmeric supplement dose. Clinical presentation was notable for diffuse plate-like yellow scaling of the scalp with lesser involvement of the ears. On the trunk and extremities, erythematous circinate plaques studded with pustules were noted with central trailing scale and desquamation. Laboratory results showed slight elevation of white blood cell count from her baseline but within normal range. Histopathological analysis of two punch biopsies showed spongiotic dermatitis with eosinophils, and subcorneal pustules with eosinophils, respectively, without any organisms. These findings were most consistent with acute generalized exanthematous pustulosis (AGEP). Treatment included oral and topical corticosteroids as well as discontinuation of all dietary supplements. AGEP, a severe cutaneous adverse reaction, is associated most often with antibiotics; however, many other medications, including herbal supplements, have been documented as triggers in the literature. This is only the second reported case of potential turmeric-induced AGEP and the first reported case establishing a dose-related association between turmeric and AGEP. It is important to consider herbal supplements as part of the medical history to guide proper management when assessing a patient with AGEP.

Acute Localized Exanthematous Pustulosis (ALEP) Caused by Topical Application of Minoxidil.

Acute Localized Exanthematous Pustulosis (ALEP) is a rare skin reaction characterized by the sudden onset of multiple, small, sterile, non-follicular pustules in an erythematous and edematous base succeeding systemic drug administration. ALEP is considered a subtype of Acute Generalized Exanthematous Pustulosis (AGEP), although the exact pathogenic mechanism of the disease remains poorly defined. Numerous drugs have been implicated in the pathogenesis of ALEP, while contact mechanisms have also been reported. Herein, we describe the first case of ALEP attributed to minoxidil in a female patient with androgenetic alopecia. The positivity of patch tests and the topical application of minoxidil proposes a contact-induced hypersensitivity reaction. Identifying new agents-including minoxidil-which serve as inducers of drug-specific T-cell-mediated responses in the clinical spectrum of ALEP, adds further value in understanding the complex, yet unknown, pathophysiological mechanisms of this rare drug hypersensitivity reaction.

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer.

Immune checkpoint blockade (ICB) improves survival in many types of cancers including melanoma, non-small cell lung, renal cell, breast, and cervical cancers. However, many of these therapies are also associated with high grade dermatologic adverse events (DAEs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), SJS/TEN-like reactions, high grade maculopapular and psoriasiform rashes, autoimmune bullous eruptions, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may limit their tolerability and use. It is important to properly identify and treat DAEs to ICB because these DAEs may be associated with positive anti-tumor response and patients may have limited options for alternative anti-cancer therapeutics. In this review, we describe high grade DAEs to increasingly used ICB agents, which target CTLA-4 and PD-1 or its ligand, PD-L1 and enable the immune system to target cancer cells. We further differentiate life-threatening adverse reactions from mimickers and report cases of serious DAEs which have been recorded in association with ICB through the FDA Adverse Events Reporting System (FAERS), which is an archive of adverse events associated with various drugs and therapeutic biologic products reported voluntarily by consumers and healthcare professionals as well as mandatorily by manufacturers. Lastly, we summarize management recommendations for these adverse events and discuss knowledge and evidence gaps in this area.

Severe Drug Hypersensitivity Reactions: Clinical Pattern, Diagnosis, Etiology and Therapeutic Options.

Severe cutaneous adverse reactions (SCAR) are known for a high morbidity and mortality. They may be life-threatening for the affected patient and difficult to accomplish for the patient's family and the treating physician. Such conditions include not only bullous reactions like toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), but also acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Since clinical pattern, etiology, prognosis and treatment differ among these severe skin reactions, a clear diagnosis based on a comprehensive clinical examination, skin biopsy, and specific laboratory tests is necessary. Because most of these reactions are caused by drug intake, a thorough history of medication use has to be obtained. However, there are cases with an infectious or idiopathic cause. In any case it is crucial to identify the most likely cause and rapidly discontinue the inducing agent, if a drug cause is suspected. This is associated with the patient`s prognosis which is often poor for bullous reaction. In addition, patient's age, underlying conditions, and the extent of skin detachment play a major role in terms of prognosis. Severe cutaneous adverse reactions are T-cell-mediated reactions, and certain alleles of human leukocyte antigens (HLA) are involved in the activation of T-cells with cytotoxic effect. The therapeutic options depend on the clinical diagnosis. For all reactions a symptomatic and adequate supportive therapy is necessary, in some cases a systemic immunomodulating therapy can be useful.

Pustular psoriasis complicated with acute generalized exanthematous pustulosis.

BACKGROUND: Pustular psoriasis of the digits (acrodermatitis continua of Hallopeau) may be localized to one or more digits for over an extended period of time. Characteristic presentation is that of tender, diffusely eroded, and fissured pustular plaques on one or more digits. Transition to other forms of psoriasis and to generalized pustular psoriasis is known to occur. These patients have an increased risk of acute generalized exanthematous pustulosis (AGEP) compared to the general population. Pustular psoriasis is often therapy resistant. MAIN OBSERVATIONS: We report the case of a 54-year-old Caucasian woman who presented with a pustular psoriasis flare complicated by AGEP. Treatment course included hospital admission, cyclosporine, acitretin, and discontinuation of cephalexin. CONCLUSION: The precipitating factor in the course of treatment is thought to be cephalexin. When treating patients with pustular psoriasis the occurrence of druginduced complications should be carefully examined. Our case suggests that avoidance of ß-lactam antibiotics in these patients is warranted unless absolutely indicated.

Acute generalized exanthematous pustulosis: A histologic study of forty-five cases

Background Literature on acute generalized exanthematous pustulosis (AGEP) is restricted to case reports, with only one prior series study. More importantly, a detailed histologic comparison to pustular psoriasis has not been done. Objective To identify discriminatory characteristics, we compared the histologic features of 45 cases of AGEP and 19 cases of pustular psoriasis. Methods Demographic, historical, clinical, and histologic features of AGEP and pustular psoriasis were compared using specimens from 5 tertiary medical centers. Results The age of patients with AGEP ranged from 12 to 91 years (mean, 53 years) with a nearly equal M:F ratio. All 45 patients presented with a generalized erythematous, pustular eruption (mean duration of pustules, 12 days) and fever (present in 25/31 patients). Recent drug ingestion was documented in 36/38 (95%) patients. Of the 5 pediatric cases, two had prior upper respiratory tract infection, but were without a history of recent drug ingestion. No patient with AGEP had a history of psoriasis. AGEP was distinguished from pustular psoriasis based upon the following histologic features: necrotic keratinocytes, papillary dermal edema, presence of eosinophils within the dermis, and absence of parakeratosis with neutrophils (p <0.05). Conclusion While the precise etiology of AGEP remains unknown, our findings confirm that most AGEP cases in adults are drug-related. Certain histologic features appear to reliably discriminate AGEP from pustular psoriasis, and awareness of them may increase diagnostic accuracy.

Two Cases of Acute Generalized Exanthematous Pustulosis / 대한피부과학회지

Acute generalized exanthematous pustulosis(AGEP) is characterized by the abrupt onset of widespread pustules on an erythematous base and rapid spontaneous healing. Most cases appear to be related to drug reactions, mainly antibiotics, viral infections, and hypersensitivity to mercury. We report two cases of acute generalized exanthematous pustulosis which presented with widespread tiny pustules on the whole body. Histopathologic examinations of both cases showed subcorneal neutrophilic pustules with perivascular polymorphous cellular infiltration. We suspected that the possible cause of two cases was inhalant mercury and carbamazepine.

Clinicopathologic Study of Generalized Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis / 대한피부과학회지

BACKGROUND: Generalized sterile pustular eruption with fever which occurs in generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis(AGEP) present a diagnostic and therapeutic problems. In Korea, there are a few studies of clinical and histopathologic reviews of these diseases, but long term follow-up and comparative clinicopathologic studies of these two diseases are not available. OBJECTIVE: This study attempts to identify the differences of these two diseases in the aspects of clinical, laboratory, and histopathologic findings. METHODS: We evaluated the clinical features, laboratory and histopathologic findings in 41 patients with generalized pustular eruption who had visited Pusan National University hospital during the past 20 years and reviewed the literature. RESULTS: 1. The ratio of patients with GPP(n=32) to ones with AGEP(n=9) was 3.6:1. 2. The mean age at diagnosis was 32.9(male) and 28.9(female) years in GPP, and 10.3 years(male) and 62.8 years(female) in AGEP. 3. The number of patients of GPP with previous personal history of psoriasis vulgaris were 15/32(46.9%) and the number of ones with previous family history of psoriasis vulgaris were 2/32(6.3%). 4. There was no patient of AGEP with personal or familial history of psoriasis. 5. The number of patients with recent drug intake history were 4/32(12.9%) in GPP and 9/9(100%) in AGEP. And common drugs suspected to cause AGEP were antibiotics(4 cases) and analgesics(3 cases). 6. Associated systemic symptoms were fever(37.5%), arthralgia(18.8%), and itching(62.5%) in GPP, whereas 66.7%, 33.3%, and 55.6%, respectively in AGEP. 7. The mean duration of pustules was 32.9 days in GPP and 7.2 days in AGEP. 8. Reccurences of generalized pustular eruption were 46.9% in GPP and 0% in AGEP. 9. Laboratory findings revealed leukocytosis(34.4%), elevated erythrocyte sedimentation rate(28.1%), hypoalbuminamia(25.0%), and eosinophilia(6.3%) in GPP, whereas 77.8%, 55.6%, 33.3%, and 71.4%, respectively in AGEP. 10. GPP and AGEP are diseases sharing similar clinical features, but these two diseases show distinctive clinical, laboratory, and histologic features. We suggest that it is important to be aware of these distinctions for avoidance of unnecessary aggressive therapy indicated for GPP.