|Year : 2018 | Volume
| Issue : 3 | Page : 414-417
|Kyrle's disease associated with HIV infection, diabetes, and chronic kidney disease
Geysa Maria Nogueira Farias1, José Reginaldo Pinto1, Juliana Carneiro Melo2, Lara Gurgel Fernandes Távora3, Danielle Malta Lima2, Fernanda Judith Viana Correia4, Geraldo Bezerra da Silva Júnior2
1 Postgraduate Program in Public Health, Health Sciences Center, University of Fortaleza, Fortaleza, Ceara, Brazil
2 Postgraduate Program in Public Health; School of Medicine, Health Sciences Center, University of Fortaleza, Fortaleza, Ceara, Brazil
3 School of Medicine, Health Sciences Center, University of Fortaleza, Fortaleza, Ceara, Brazil
4 Cancer Institute of Ceara, Haroldo Juacaba Hospital, Fortaleza, Ceara, Brazil
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|Date of Web Publication||13-Jul-2018|
| Abstract|| |
Kyrle's disease (KD) is a rare skin pathology characterized by transepidermal elimination of abnormal keratin. The aim of this article is to report a rare case of KD associated with diabetes mellitus, chronic kidney disease, and HIV. A 51-year-old male patient complained of diarrhea for 8 months. He was submitted to HIV testing, which showed a positive result. He started antiretroviral therapy with zidovudine, lamivudine, and lopinavir. The diagnostic investigation was negative for opportunistic diseases. After 2 months, skin lesions started appearing, characterized by hyperchromic, pruritic macules and papules distributed in the trunk, back, and upper limbs. He also developed erythematous, scaly lesions in the facial region. A biopsy of the skin was performed, of which histopathological report consisted of perforating disorder, favoring a diagnosis of KD. Treatment with keratolytic soap (Actine) was started, with skin lesion improvement. In this reported case, it is possible that, in addition to diabetes and renal failure, HIV infection played an important role in the genesis of the lesions.
Keywords: Diabetes, HIV, kidney disease, Kyrle's disease, rare diseases
|How to cite this article:|
Nogueira Farias GM, Pinto JR, Melo JC, Fernandes Távora LG, Lima DM, Viana Correia FJ, da Silva Júnior GB. Kyrle's disease associated with HIV infection, diabetes, and chronic kidney disease. Indian J Pathol Microbiol 2018;61:414-7
|How to cite this URL:|
Nogueira Farias GM, Pinto JR, Melo JC, Fernandes Távora LG, Lima DM, Viana Correia FJ, da Silva Júnior GB. Kyrle's disease associated with HIV infection, diabetes, and chronic kidney disease. Indian J Pathol Microbiol [serial online] 2018 [cited 2020 Feb 19];61:414-7. Available from: http://www.ijpmonline.org/text.asp?2018/61/3/414/236615
| Introduction|| |
Kyrle's disease (KD) is a rare skin disease characterized by transepidermal elimination of abnormal keratin. It has been described as one of the perforating dermatosis subtypes along with reactive perforating collagenosis, serpiginous perforating elastosis, and perforating folliculitis. KD is considered a genetically determined, adult-onset disease, usually starting between 30 and 50 years of age, being more prevalent in female patients.
It presents as multiple erythematous papules with a central depression area covered by a crust, frequently affecting the lower limbs. Keratinolytic agents are the drugs of choice for the initial treatment of KD (salicylic acid and urea), followed by cryotherapy and laser surgery. Antibiotic therapy and local and systemic treatment with Vitamin A acid may also be used. It has been reported that tetracycline and tacalcitol promote the keratinization process.
Although it was described almost a century ago, the etiology of KD is still unknown. Some authors consider it an autosomal dominant or recessive genodermatosis. Other studies claim that it may rarely be an idiopathic or hereditary disease. However, several conditions are associated to its occurrence, and among them are diabetes mellitus, chronic kidney disease (especially in patients on hemodialysis), liver failure, and heart failure. The association of KD with some infectious diseases such as viral hepatitis, tuberculosis, pulmonary aspergillosis, and scabies has also been described.
There are few case reports describing the occurrence of primary perforating dermatosis in association with HIV infection. Cases of reactive perforating collagenosis and perforating folliculitis have been described. The association between KD and HIV infection is still unknown.
The aim of this article is to report a rare case of KD associated with diabetes mellitus, chronic kidney disease, and HIV. The patient has signed consent form authorizing this publication.
| Case Report|| |
A 51-year-old male patient sought medical care due to persistent diarrhea for approximately 8 months. He underwent digestive endoscopy and colonoscopy, and gastritis caused by Helicobacter pylori and right colitis was identified. He was prescribed omeprazole and amoxicillin + clarithromycin for the treatment of H. pylori infection. He also reported weight loss (10 kg in the last 5 months). At physical examination, the patient was pale, eupneic, without lymphadenomegaly, with normal cardiopulmonary auscultation, adbomen with palpable liver and spleen, and discrete lower limbs edema.
He underwent Human Immunodeficiency Virus (HIV) testing, which was positive. He started antiretroviral therapy with zidovudine, lamivudine, and lopinavir. The diagnostic investigation was negative for opportunistic diseases. Hypertension, diabetes, and kidney disease (glomerular filtration rate of 27 mL/min) were also diagnosed. Although the treatment for diabetes mellitus (acarbose, NPH, and regular insulin) was started, the patient persisted with high blood glucose levels. After 5 months, he developed a worsening of renal function and started dialytic treatment. After 2 months, skin lesions started appearing, characterized by hyperchromic, pruritic macules, and papules distributed in the trunk, back, and upper limbs. He also developed erythematous, scaly lesions in the facial region. At the time, laboratory tests showed CD4+ T lymphocytes of 225 cells/dL, viral load of 48 copies/mL, blood glucose of 142 mg/dL, glycated hemoglobin of 6.1%, creatinine of 3.22 mg/dL, and urea of 104 mg/dL.
Skin biopsy of the back was performed, represented by an irregular fragment of brown skin, measuring 0.5 cm × 0.3 cm × 0.2 cm, with no apparent lesions. Microscopic examination of skin sample showed keratin-filled follicle with parakeratosis, loss of continuity areas with moderate-mixed inflammatory infiltrate, vascular and conjunctive neoformation, and multinucleated foreign-body giant cells around the follicle [Figure 1] and [Figure 2]. The conclusion of the histopathological report was perforating disorder, favoring a diagnosis of KD.
|Figure 1: Panoramic view of the lesion, highlighting the dilated hair follicle (H and E, ×3.5) (Pannoramic Viewer 1.15)|
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|Figure 2: Lesion detail: dilated hair follicle filled with keratin and mixed inflammatory infiltrate with multinucleated foreign-body giant cells around the follicle (H and E, ×10) (Pannoramic Viewer 1.15)|
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Treatment with keratolytic soap (Actine) was started, with skin lesion improvement.
| Discussion|| |
The present case illustrates a rare association between KD (acquired perforating dermatosis), HIV infection, diabetes mellitus, and chronic kidney disease. The perforating disorders observed in the end-stage renal patient share characteristics similar to that of primary perforating dermatoses such as KD, perforating folliculitis, and reactive perforating collagenosis.
KD has two distinct forms: a hereditary form that starts in childhood and an acquired form that usually develops in adulthood, more commonly in women between 30 and 50 years of age associated with some underlying systemic disorder. KD is present in 21% of these individuals, especially African-Americans, and is associated with diabetes mellitus. The most common location is in buttocks and extremities. The clinical picture is characterized by papules of 2–8 mm in diameter, with keratotic tamponade, and some coalescing into plaques. The lesions may be follicular or extrafollicular, and the linear arrangement is common. Regarding the patient reported in this article, the lesions predominated in the trunk and back, being characterized by pruritic macules and papules.
The histological analysis discloses the presence of a parakeratotic plug, consisting of basophilic debris and epidermal depression with or without follicular involvement. Usually, it shows acanthosis around the epidermis, dyskeratosis, and vacuolated epidermal cells, adjacent to the parakeratotic column. Dilated follicular infundibulum caused by parakeratosis, orthokeratosis, and basophilic degeneration also occurs. In this pathology, the dyskeratotic cells develop at multiple points within the epidermal invaginations. These cells have limited capacity to proliferate but maintain accelerated rates of keratinization. This causes a defect in the epidermis, and the rapid keratinization perforates the dermis, causing a granulomatous inflammatory response.
Subsequent reepithelialization of the adjacent epidermis over the entire process occurs from the bottom up. The dermal connective tissue, together with inflammatory and keratotic debris, degenerates to form the basophilic debris, which corresponds to the keratotic tamponade. This is exuded from the invagination seen in the fully developed form of the lesion. In the case reported, the presence of keratin-filled hair follicles with parakeratosis, area of solution of continuity with moderate-mixed inflammatory infiltrate, and multinucleated foreign-body giant cells around the follicle was observed, suggesting the diagnosis of KD. KD should be differentiated from other classic perforating dermatoses. In cases of perforating folliculitis, epidermal invagination is observed in relation to a vellus hair, which was absent in our case. In serpiginous perforating elastosis, there are thickened elastic fibers around the epidermal invagination. Reactive perforating collagenosis was also ruled out due to the absence of degenerated collagen at the perforation base.
The differential diagnosis is made through a clinical-pathological correlation with other keratinization disorders such as pityriasis rubra pilaris type I, Darier's disease, Flegel disease, hyperkeratosis lenticularis perstans, disseminated superficial actinic porokeratosis, hypertrophic and verrucous lichen planus, and other classic perforating dermatoses, among which perforating folliculitis is highlighted, as described above.
In diabetic patients, insulin administration and glycemic stabilization resulted in disease regression. The hypoglycemic effect and anti-inflammatory nature of insulin may result in improved symptoms of the disease. The pathogenesis associated with diabetes mellitus is unknown. It may be a result of changes in the epidermis or dermis leading to metabolic changes and a skin response to superficial trauma and vasculopathy due to oxidative damage or endoplasmic stress as products of advanced glycation and oxidized low-density lipoprotein end products. In the case reported, the patient showed persistently elevated glycemic levels, despite the implemented treatment, and this alteration could be related to cell oxidative damage, making him more susceptible to the development of KD.
In a study of 99 patients with chronic kidney disease evaluated with skin diseases, acquired perforating disorders (APDs) such as perforating folliculitis, KD, and reactive perforating collagenosis were found. We found KD in 17 (17.17%) patients, of which 12 (12.12%) were undergoing maintenance hemodialysis. APDs have been identified in 4.5%–10% of patients undergoing maintenance hemodialysis. The abundance of polymorphonuclear neutrophil debris in the early stages of these diseases has led to the assumption that neutrophil cell dissolution, with the release of proteolytic enzymes, including the elaboration of collagenase and elastase, may initiate the pathological process. In the reported case, the patient had high urea and creatinine values since the start of his follow-up (March 2013), which may have contributed to the development of KD.
Other infectious and chemical agents have also been shown to cause KD, and the infectious origin of the disease is justified by the fact that antibiotic therapy results in lesion regression. Good responses to oral clindamycin (300 mg) administered three times a day for 1 month have been described. Treatment discontinuation usually results in recurrent lesions.
In the reported case, it is possible that, in addition to diabetes and kidney disease, HIV infection has played an important role in the genesis of the lesions. It has been suggested by some authors that a competent immune response is not essential for the transepidermal elimination of substances to occur since even HIV-positive patients with significant immunosuppression can manifest this phenomenon, both in the context of perforating dermatoses and of other diseases.
In HIV-positive immunocompromised patients, there is a decrease in the number and function of antigen-presenting cells and CD4+ T lymphocytes, making the skin more vulnerable to opportunistic and neoplastic infectious agents. This may be one of the explanations for KD manifesting in immunocompromised patients.
| Conclusion|| |
In the reported case, the patient presented with immunosuppression and failure in virological control at the time of KD diagnosis, which raises the question about the importance of immunosuppression in the pathogenesis of this disease.
Informed consent was obtained from the patient in this case report.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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Geraldo Bezerra da Silva Júnior
Av. Washington Soares, 1321, Bloco S-01, CEP 60811-905, Fortaleza, Ceará
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]