Axillary granular parakeratosis
Axillary Granular Parakeratosis
Are You Confident of the Diagnosis?
What you should be alert for in the history
Patients present with pigmented, moist, pruritic plaques in the folds of skin; most commonly, the axillary creases. Authors have suggested the term “granular parakeratosis” be used because the condition may affect other sites, such as the inguinal folds.
Characteristic findings on physical examination
The most common findings are unilateral or bilateral, pruritic, axillary erythematous hyperpigmented patches/plaques with a moist brown appearance (
A characteristic red-brown scaly plaque of granular parakeratosis.
Typical location, with red-brown appearance of moist hyperkeratosis.
Expected results of diagnostic studies
Biopsy is classic, revealing hyperkeratosis with the maintenance of keratohyalin grannules in the stratum corneum.
Biopsy is the definitive method of diagnosis. The differential diagnosis includes: intertrigo, Hailey-Hailey disease (benign familial pemphigus), pemphigus vulgaris and pemphigus vegetans, Bowen's disease, tinea cruris, and acanthosis nigricans. These can be distinguished by history, physical examination and response to therapy.
Intetrigo is generally found in other areas at the same time, including groin and inframammary areas, and responds well to topical therapy and/or oral azoles for short courses.
Hailey-Hailey disease generally occurs in other intertriginous areas at the same time and also has a familial tendency. Pemphigus vulgaris is generally in mucosal areas as well as on the skin and tends to be more painful than pruritic.
Bowen's disease is usually unilateral and has a more prolonged course prior to presentation. Tinea cruris is generally more erythematous and scaly, KOH positive, and responsive to topical therapy. Acanthosis nigricans is usually pigmented with granular parakeratosis, but is generally seen in other areas, such as the nape of the neck; it is characteristically asymptomatic and chronic.
Who is at Risk for Developing this Disease?
The usual patient is overweight or has chronic moisture in the intertriginous areas.
What is the Cause of the Disease?
The etiology is unknown, but is thought to be due to an extrinsic stimulus, such as deodorant.
The extrinsic stimulus is thought to produce epidermal proliferation that maintains both the nuclei and keratohyalin granules in the stratum corneum by blocking the formation of filaggrin from profilaggrin. There is also a proposed mechanism that a basic defect in processing profilaggrin to filaggrin results in a failure to degrade keratohyalin granules and aggregate keratin filaments during cornification.
Systemic Implications and Complications
There is no significant association with systemic disease.
Therapeutic options include
Weight loss and use of less deodorant
Antifungals (eg, ketoconazole and econazole); combination antifungal and low-potency topical steroids (eg, desonide or alclometasone); topical retinoids (eg, tazarotene and tretinoin), vitamin D analogs such as calcipotriene, ammonium lactate, and botulinum toxin A.
Azoles and isotretinoin such as fluconazole 100mg daily with food for 2 weeks or isotretinoin 20-40g/day for 2-4 weeks.
Optimal Therapeutic Approach for this Disease
The optimal therapeutic ladder includes those treatment options noted above, with most patients responding to topical antifungal/steroid combinations as well as a reduction in the quantity and frequency of deodorant/powder agents. Most patients will respond in 1-2 weeks.
If no improvement is seen with this option, then one might consider the addition of an oral azole for 1-2 weeks. The next option would be the use of a topical retinoid, which may do well, but is sometimes irritating and needs to used less often or in conjunction with a mild topical steroid (Class V or VI). Lastly the use of oral isotretinoin for 1-2 weeks may have a dramatic effect. There is a case report of botulinum toxin type A demonstrating benefit in one patient as well.
Patients should be counseled on excessive use of topical deodorants/antiperspirants in the involved areas well as maintaining a dry environment as much as possible.
Unusual Clinical Scenarios to Consider in Patient Management
Patients not responding to standard techniques should be rebiopsied for routine microscopy and/or direct immunofluorescence to rule out immunobullous diseases or Bowen's disease.
What is the Evidence?
1. Northcutt, AD, Neson, DM, Tschen, JA. "Axillary granular parakeratosis". J Am Acad Dermatol. vol. 24. 1991. pp. 541-4.(This article is one of the first to describe axillary granular parakeratosis and its potential pathophysiology. The authors describe the condition and its potential to be induced by extrinsic factors such as deodorants. They also suggest that the offending agent may alter the maturation sequence of the stratum granulosum and stratum corneum by interfering with the degradation of filaggrin precursors.)
2. Wallace, CA, Pichardo, RO, Yospovitch, G. " Granular parakeratosis: a case report and literature review". J Cutan Pathol. vol. 30. 2003. pp. 332-5.(This article is another case report and review of the literature. The authors suggest an irritant contact source as the potential causative factor.)
3. Metze, D, Rutten, A. "Granular parakeratosis-a unique acquired disorder of keratinization". J Cutan Pathol. vol. 26. 1999. pp. 339-52.(This article describes 10 cases of axillary granular parakeratosis as well as a detailed description of the histopathology and the inflammatory infiltrate of these cases. The authors also speculate that a failure to degrade keratohyalin granules is an underlying mechanism.)
4. Contreras, ME, Gottfired, LC, Bang, RH. " Axillary intertriginous granular parakeratosis responsive to topical calcipotriene and ammonium lactate". Int J Dermatol. vol. 42. 2003. pp. 382-3.(This case report describes resolution with the combination of topical calcipotriene and ammonium lactate.)
5. Scheinfeld, NS, Mones., J. "Granular parakeratosis: pathologic and clinical correlation of 18 cases". J Am Acad Dermatol. vol. 52. 2005. pp. 863-7.(This report and review of 18 cases describes the incidence of axillary granular parakeratosis as .0005% of pathology cases seen at the Ackerman Institute of Dermatopathology. All patients were adults and most were women. Out of the 18 cases, only one was submitted with the correct clinical diagnosis, allowing the authors to conclude that dermatologists were not very familiar with this uncommon condition.)
6. Ravitskiy, L, Heymann, WR. "Botulinum toxin-induced resolution of axillary granular parakeratosis". Skinmed. vol. 4. 2005. pp. 118-20.(This case report describes rapid resolution of axillary granular parakeratosis in a few days after using botulinum toxin type A. The patient was previously unresponsive to mid-potency topical steroids.)
7. Brown, SK, Heilman, ER. "Granular parakeratosis: resolution with topical tretinoin". J am Acad Dermatol. vol. 47. 2002. pp. S279-80.(This case report describes a single case of axillary granular parakeratosis responding to topical tretinoin.)
8. Webster, CG, Resnik, KS, Webster, GF. "Axillary granular parakeratosis: response to isotretinoin". J Am Acad Dermatol. vol. 37. 1997. pp. 789-90.(This case report describes a rapid resolution of axillary granular parakeratosis with 3 weeks of isotretinoin 40mg daily).
9. Comption, AK, Jackson, JM. "Isotretinoin as a treatment for axillary granular parakeratosis". Cutis. vol. 80. 2007. pp. 55-6.(This case report describes rapid resolution of axillary granular parakeratosis with 2 weeks of isotretinoin 40mg daily.)
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