Hyperkeratotic flexural erythema (more commonly known as granular parakeratosis) with use of laundry sanitizers containing benzalkonium chloride.

BACKGROUND: Hyperkeratotic flexural erythema (HKFE), also known as granular parakeratosis, is a scaly, erythematous or brown eruption, which usually occurs in the intertriginous and flexural areas. It has been linked to the use of benzalkonium chloride (BAK). AIM: To review the clinical presentation of patients diagnosed with HKFE who had been exposed to laundry sanitizer containing BAK, and the therapies trialled to treat these patients. METHODS: This was a retrospective cases series of 45 patients seen by dermatologists in Victoria, Australia. Information was collected on clinical presentation, investigation and management. RESULTS: The patients varied in age from 18 months to 89 years. The rash typically presented as a symmetrical erythema with characteristic multilayered brownish epidermal scaling. The most common location of the rash was the inguinal/anogenital area (32 of 45 patients; 71.1%) and there was a female predominance. Regarding treatment, topical corticosteroids were frequently prescribed and antibiotics were trialled in 11 patients; however, the condition resolved spontaneously over time in all patients with use of emollients, along with cleaning of the washing machine by running an empty wash, and repeated washing or sometimes disposal of BAK-contaminated clothing. CONCLUSION: This large case series highlighted the characteristic clinical presentation of HKFE in the setting of BAK used in laundry sanitizer, demonstrating a potential causal link. Further studies are required to evaluate the role of the skin microbiome.

Axillary Granular Parakeratosis.

We describe a case of an 85-year-old Caucasian female who presented to the dermatology clinic with pruritic, scaly hyperpigmented papules and plaques with surrounding erythema in the left axilla. Based on the history and physical examination, there was concern for possible varicella zoster infection, and the patient was started on valacyclovir 1000 mg three times daily for seven days. A shave biopsy was taken from the left axilla to confirm a diagnosis. Microscopic examination revealed compact hyperparakeratosis with keratohyalin granules throughout the parakeratotic stratum corneum as well as admixed eosinophils within the stratum corneum. The epidermis was acanthotic with irregular hyperplasia of the rete ridges. These microscopic findings supported a diagnosis of axillary granular parakeratosis, a benign skin condition caused by a defect in epidermal differentiation. Granular parakeratosis is seemingly rare but is felt to be an underreported condition. It is important for clinicians to be aware of the disease in order to correctly identify the lesions and reassure patients of its benign nature and provide appropriate treatment recommendations.

Photodynamic Therapy, a successful treatment for granular parakeratosis.

Granular parakeratosis is characterized by variably hyperkeratotic brownish papules or plaques, mostly found on flexures. Different treatments have been suggested with variable results. We present a series of 3 cases successfully treated with one session of methyl-aminolevulinate photodynamic therapy, showing resolution of the lesions and symptoms within less than 2 weeks, as a potentially new, safe and effective therapeutic option.

[Spiny hyperkeratosis of the palms and soles]. / Spiny Hyperkeratosis palmaris et plantaris.

Spiny hyperkeratosis of the palms and soles is a rare dermatosis presenting as multiple tiny keratotic plugs on the palms and soles. There are two different forms of spiny keratoderma of the palms and soles - the hereditary form and the acquired form. The latter is usually associated with internal malignancies or systemic disease. Since spiny hyperkeratosis of the palms and soles has been under-reported and under-diagnosed, it is important for dermatologists not to forget this disease in daily practice. We report this rare disease for the first time in the German literature.

Clinical features, histology, and treatment outcomes of granular parakeratosis: a systematic review.

BACKGROUND: Granular parakeratosis is a rare disorder characterized by erythematous-brown hyperkeratotic papules and erythematous patches with scaling, occurring predominantly in the flexures and sites of occlusion. While the exact underlying pathogenesis remains unknown, there has been a wide variety of precipitating factors and treatment options reported in the literature. OBJECTIVE: We systematically reviewed and identified precipitants of granular parakeratosis, as well as its clinical and histologic features and treatment outcomes. METHOD: A comprehensive literature search was conducted using MEDLINE and Embase in March 2021. RESULTS: A total of 60 studies with 129 patients were included for analysis. An inciting factor was identified in 53.4%, the most common being topical agents including zinc oxide (17.1%), deodorant/antiperspirant (15.5%), and those containing benzalkonium chloride (7.0%). The majority presented with bilateral (68.2%) eruption of hyperkeratotic papules or erythematous patches and plaques, most frequently involving the axilla (56.5%). The prevailing histologic feature was retained keratohyalin granules within the stratum corneum in punch biopsy (97.2%) and curette (100%) specimens. Treatment options with reported success ranged from topical corticosteroids and systemic antibiotics to surgical interventions. CONCLUSION: We provide a systematic review of reported precipitants, clinical features, and treatment options that clinicians should consider when granular parakeratosis is considered.

Effects of a moisturizer containing pseudo-ceramide and a eucalyptus extract on sweating function in adult atopic dermatitis: a double-blind, randomized, controlled left-right comparison clinical trial.

BACKGROUND: Many patients with atopic dermatitis (AD) have a decreased ability to sweat. Several factors can cause decreased perspiration, such as weak tight junctions of sweat ducts, reduced acetylcholine receptor function, and inhibition of perspiration by histamines. Parakeratosis of AD skin also decreases sweating by occluding sweat pores. Increased ceramide levels in the stratum corneum reduce parakeratosis by improving stratum corneum functions. Furthermore, ceramides and/or ceramide derivatives may affect claudin-3 and acetylcholine receptors. OBJECTIVE: In this study, we investigated the efficacy of a moisturizer containing pseudo-ceramide and a eucalyptus extract to increase ceramide levels in the epidermis to improve the sweating ability of patients with AD. METHODS: Nineteen patients with AD applied moisturizers with or without pseudo-ceramide and a eucalyptus extract on the cubital fossa of either arm twice a day for 4 weeks. Skin conditions and sweating ability, measured as the response to acetylcholine stimulation, were evaluated prior to the start of the study (Week 0) and at the end of Weeks 2 and 4. RESULTS: Both moisturizers improved the visually evaluated skin symptoms and skin hydration. However, only the moisturizer containing pseudo-ceramide and the eucalyptus extract significantly improved cutaneous barrier function and significantly increased the ceramide level in the stratum corneum. That moisturizer also increased the sweating volume and shortened the latency time for sweating, an indicator of sweating ability, but the other moisturizer did not. CONCLUSION: Based on these results, the moisturizer containing pseudo-ceramide and a eucalyptus extract helps recover the sweat function of AD patients.

Efficacy study of vesicular gel containing methotrexate and menthol combination on parakeratotic rat skin model.

Methotrexate (MTX) is indicated in the symptomatic control of severe, recalcitrant, and disabling psoriasis. The oral or parenteral route of administration causes systemic toxicity. The topical route of delivery, though, reduces systemic toxicity and has limited applicability due to restricted permeability. Liposomal and niosomal MTX topical formulations have also been investigated with limited success to achieve drug localization in the skin. Menthol has been suggested in conditions of psoriasis, in addition to its skin-penetration-enhancing effect on drugs. The present work aimed at investigating the potential benefits of combining menthol with MTX in a vesicular gel base for not only improving the penetration and dermal availability of MTX, but also to render such a formulation more effective with greater patient acceptability. MTX liposomes were prepared by thin-film hydration, and the vesicles were characterized for drug-entrapment efficiency, size, and morphology. These liposomal vesicles were incorporated in a gel base, and this vesicular gel was evaluated for transdermal drug permeation and extent of drug accumulation in the skin, using a rat skin ex vivo model. Skin histology studies were carried out to investigate any structural changes caused by the permeation enhancers. Antipsoriatic efficacy of the formulations was tested in vivo, using the rat tail model. The results indicated that the vesicular gel containing menthol could cause maximum drug retention in the skin. The skin treated with menthol had a disrupted epidermis and microcavities. The in vivo studies also ascertained the effectiveness of the formulation in inducing a normal pattern of differentiation in the rat tail skin that initially showed parakeratosis, which is also characteristic of psoriatic epidermis. These results show the potential of vesicular gel containing MTX and menthol to improve penetration into the skin and cause drug retention in skin appendages.

Granular parakeratosis: response to calcipotriene and brief review of current therapeutic options.

A 34-year-old Hispanic woman presented with an 18-month history of an intermittent, asymptomatic eruption that began on her left axilla after using a depilatory cream containing corn starch and thioglycolate (Figure 1A). The eruption then spread to her right axilla and lower abdomen (Figure 1B). She reported worsening with deodorant use, but had been using the same deodorant for many years and had continued using it twice a day. Treatment with topical corticosteroids had not helped. The patient coincidentally had been started on isotretinoin 5 months previously for acne, but it had no effect on her axillary or abdominal lesions. Physical examination revealed multiple dark brown and black papules with a "stuck-on" appearance in both axillae and on the lower right abdomen. A biopsy of the left axilla revealed a thickened parakeratotic stratum corneum with retention of keratohyalin granules within the parakeratoric cells, which is considered diagnostic of granular parakeratosis (Figure 2). The patient was prescribed calcipotriene cream twice daily. After 2 weeks, she had complete resolution of the axillary lesions, but the abdominal lesions persisted. She has since had mild recurrences while using calcipotriene.

Punctate porokeratotic keratoderma.

We report a 29-year-old woman with multiple small keratotic papules on her lateral fingers and first and second toes. Histopathology revealed a compact parakeratotic column with a poorly developed stratum granulosum, indicating punctate porokeratotic keratoderma (PPK). We discuss demographics, etiology, histopathology, differential diagnosis, and treatment of this disease.

Ichthyosiform sarcoidosis: A case report and review of the literature.

Sarcoidosis is a potentially life-threatening, multisystem, granulomatous disease that can present with cutaneous manifestations in patients. A rare cutaneous manifestation of this disease may resemble acquired ichthyosis. We report a 45-year-old woman with a several year history of dyspnea on exertion and panuveitis who presented to a county hospital with acquired lower extremity ichthyosis and a biopsy consistent with both acquired ichthyosis and noncaseating, granulomatous sarcoidosis. To our knowledge, this entity has been described in only 22 previous independent cases, with the present case being 1 of only 5 cases to rapidly progress to full systemic involvement. Furthermore, it is important to recognize the manifestations of sarcoidosis in the skin, because these may be the presenting signs of systemic illness.

Development of Topical Gel of Methotrexate Incorporated Ethosomes and Salicylic Acid for the Treatment of Psoriasis.

BACKGROUND: There is an unmet need for optimized drug delivery system of psoriasis therapy because of various issues like adverse reaction, permeation problem associated with convention treatment (oral and topical) available for psoriasis. OBJECTIVE: The goal was to develop an ethosomal gel of methotrexate (MTX)-incorporated ethosomes and salicylic acid (SA) and to evaluate and study its ethosomal gel potential in Imiquimod-induced psoriasis animal model to treat symptoms of psoriasis. METHODS: MTX-SA ethosomal gel was prepared by the cold method given by Touitou et al. and optimized by comparing it with MTX ethosomal gel and drug solution. Particle size, zeta potential, entrapment efficiency, and ex-vivo study were selected as the critical quality checking attributes. Psoriatic Area and Severity Index (PASI) score & histopathological examination were done for checking Antipsoriatic potential of MTX-SA ethosomal gel by using the imiquimod-induced psoriasis model. RESULTS: Optimized MTX-SA exhibited a particle size of 376.04 ± 3.47nm, EE(Entrapment efficiency) of 91.77 ± 0.02%. At the end of 24h, MTX-SA ethosomal gel exhibited a slow and prolonged release of MTX (26.13 ± 1.61% versus 6.97 ± 0.06%) compared to MTX drug solution. It also attributes of 43% retention study as compared to drug solution (13%). Besides, it essentially decreased the PASI score with the recuperation of normalcy of the mice's skin, while the MTX-SA gel displayed indications of gentle hyper and parakeratosis toward the completion of investigation when contrasted with the blank gel. CONCLUSION: The developed MTX-SA ethosomal gel formulation can be a promising alternative to existing MTX formulation in topically treating psoriasis.

Isotretinoin as a treatment for axillary granular parakeratosis.

Granular parakeratosis is a condition presenting with hyperkeratotic plaques and papules that are confined to intertriginous body sites. The exact etiology is unknown, but chemical and mechanical irritation and a moist environment are potential factors. Numerous treatments have been attempted, yielding variable results. We present a case of axillary granular parakeratosis, previously unresponsive to topical treatment, that resolved after a 2-week regimen of isotretinoin. We conclude that treatment of axillary granular parakeratosis with isotretinoin is rapid and effective and should be considered in patients with no other contraindications to isotretinoin.

Botulinum toxin-induced resolution of axillary granular parakeratosis.

A 44-year-old woman presented with an 18-month history of a pruritic dermatitis in the axillae bilaterally, beginning in the springtime. There was no history of significant hyperhidrosis. The patient did not recall any change in deodorant, soap, detergent, or other topical products. Her family history was unremarkable for anyone with similar symptoms. Physical examination revealed hyperpigmented plaques on an erythematous base in both axillae. The inframammary and intertriginous folds were free of lesions. Histologic examination taken from the left axilla was notable for mild digitate papillomatosis, compact hyperparakeratosis with large nuclei, and retained keratohyaline granules within the stratum corneum (Figure), consistent with axillary granular parakeratosis. A periodic acid-Schiff stain was negative for hyphae. Patch testing utilizing the thin-layer rapid-use epicutaneous test (T.R.U.E. Test, Mekos Laboratories, Hillerod, Denmark) was unremarkable. The patient was initially treated with fluticasone propionate 0.05% cream without notable improvement. She then received Clostridium botulinum type A neurotoxin injections to the axillae (50 U/axilla) with complete resolution of the rash within a few days. At 6-months' follow-up, the patient remained asymptomatic.

Granular Parakeratosis: A Comprehensive Review and a Critical Reappraisal.

Granular parakeratosis (GP) is a rare, idiopathic, and benign skin condition that presents classically as erythematous to brown hyperkeratotic papules that can coalesce into plaques. Axillary GP was initially observed by Northcutt and colleagues and has since been described in various other areas of the body including other intertriginous and non-intertriginous sites. The term "granular parakeratosis" is now used to describe not only the skin condition, but also a distinctive histological reactive pattern on biopsy specimens that are either regarded as the disease itself, or merely as an incidental finding. Upon review of the current findings, opinions, and associations of this entity, we propose the reappraisal of GP as a reactive pattern, rather than a distinct entity.

Caso de paraqueratosis pustulosa: entidad poco frecuente y síntoma de enfermedad inflamatoria del aparato ungueal en pacientes pediátricos / Case of pustular parakeratosis: a rare entity common and symptom of inflammatory disease of the nail apparatus in pediatric patients

La paraqueratosis pustulosa es una entidad poco descrita en la literatura y se define como un proceso inflamatorio cutáneo, ungueal y periungueal en el área distal de un dedo habitualmente pulgar o índice, frecuentemente en la infancia. Su evolución suele ser benigna y la respuesta a emolientes tópicos es favorable. A continuación, se presenta un caso de esta enfermedad con el objetivo de resaltar su consideración en patologías ungueales pediátricas.

Pustular parakeratosis is an entity scantly described in literature. It has been described as a skin, nail, and periungual inflammatory process in the distal area of a finger, usually the thumb or index finger, frequently in childhood. Its evolution is usually benign and management is favorable with topical emollients. A clinical case is presented, to raise awareness of this entity in pediatric nail pathologies.

Naltrexone for treatment of acral lick dermatitis in dogs.

Acral lick dermatitis (lick granuloma) was diagnosed in 11 dogs on the basis of history, physical examination, and histopathologic findings. A predilection for the left forelimb was noticed. All 11 dogs were given the narcotic antagonist naltrexone. Successful treatment (cessation of licking, reepithelialization of lesions) was seen in 7 dogs. All 7 dogs' lesions recurred when naltrexone was stopped, but reepithelialized in 5 dogs when the drug was readministered. Adverse effects (drowsiness, withdrawal from owner) were seen in 1 dog, but resolved within 48 hours of stopping the drug.

[Axillary granular parakeratosis]. / Paraqueratosis granulosa de la axila.

Axillary granular parakeratosis is an alteration of keratin characterized by a thick parakeratotic horny layer with abundant intracellular keratohyalin granules. It was first described in 1991 and since then 32 cases have been reported from USA, Europe and Australia. Lesions may affect intertriginous areas other than the axilla. The disease has apparently not been previously described in Latin America. Three overweight Colombian women were diagnosed with axillary granular parakeratosis. They presented encrusted, hyperkeratotic, hyperpigmented and pruriginous papules and plaques which affected both axillae in two women and only one in the other. Lesions had persisted for two and four months in two patients and for one year in the third. Clinical diagnoses were benign familiar pemphigus and tinea nigra. Skin biopsies showed a thick parakeratotic basophilic horny layer. Electron microscopy demonstrated a high content of keratohyalin granules. No Langerhans cells were demonstrated in the lesions using IHC for S-100 protein. No fungi were seen with the PAS stain. Infundibula showed thick horny plugs with changes similar to those seen in the epidermis. Dermal tissue showed few perivascular lymphocytes. These findings suggest that the disease has an irritative pathogenesis. Clinical histories indicated that the three women were overweight and used several types of antiperspirants. These factors plus local irritation and humidity apparently triggered the keratinization response.