Alopecia mucinosa: report of a case and review

Case Reports

Alopecia Mucinosa: Report of a Case and Review

DOI: 10.1007/s10227-002-0103-8 J Cutan Med Surg 2003; 124–128

Bryan E. Anderson, Christine L. Mackley, and Klaus F. Helm

Abstract Background: Alopecia mucinosa has been shown to be associated with many benign and malignant conditions. It can be seen in childhood but is seen more commonly in adulthood. Alopecia mucinosa is generally felt to occur in three settings: a primary idiopathic form, a form associated with malignancy, and a form secondary to inflammatory conditions. The histologic hallmark is the accumulation of mucin in the follicular epithelium, called follicular mucinosis. Therapy for alopecia mucinosa remains problematic. Objective: We present a representative case of alopecia mucinosa and discuss the etiology, histology, epidemiology, treatment, and prognosis. Conclusion: We report a case of idiopathic alopecia mucinosa that responded to minocycline with a complete remission and we review the literature on alopecia mucinosa.

Sommaire Ante´ce´dents: La mucinose folliculaire semble associe´e a` des maladies autant be´nignes que graves. Bien qu’elle puisse apparaitre chez les enfants, elle est plus fre´quente chez les adultes. La mucinose folliculaire se manifeste ge´ne´ralement sous trois formes: une forme idiopathique primaire; une forme associe´e a` des tumeurs malignes et une forme conse´cutive a` des maladies inflammatoires. Le signe histologique premier est l’accumulation de mucine dans l’e´pithe´lium folliculaire, d’ou` son nom. Le traitement de la mucinose folliculaire reste proble´matique. Objectif: Nous pre´sentons un cas repre´sentatif de mucinose folliculaire et en examinons l’e´tiologie, l’histologie, l’e´pide´miologie, le traitement et le pronostic. Conclusion: Nous rapportons un cas de mucinose folliculaire primaire, traite´e a` la minocycline et gue´rie, et passons en revue les articles portant sur cette maladie.

A

lopecia mucinosa was first described by Hermann Pinkus in 1957.1 His original report presented six patients. The pathologic features of these patients showed a unique type of follicular degeneration with accumulation of mucin and alopecia.1 Pinkus noted that the condition occurred as solitary or multiple plaques, and if a plaque occurred on terminal hair-bearing skin, alopecia was prominent.

Department of Dermatology, Penn State College of Medicine, Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania, USA Online publication: 27 Novemnber 2002 Correspondence to: Bryan E. Anderson, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, Department of Dermatology HU14, UPC II, Suite 4300, 500 University Drive. P.O. Box 850, Hershey, PA 17033-0850, USA, E-mail: [email protected]

124

Much has been learned and written about since Pinkus’ report. Confusion and controversy still exist when discussing alopecia mucinosa (follicular mucinosis). The two terms, alopecia mucinosa and follicular mucinosis, are somewhat confusing. According to some authors the term follicular mucinosis should be applied to the histological pattern, and the term alopecia mucinosa should be used to describe the clinical dermatoses.2 Therefore, hair loss secondary to follicular mucinosis is called alopecia mucinosa. Nevertheless, in practice and in the literature these two terms are used interchangeably. Follicular mucinosis is in itself a benign inflammatory reaction pattern; however, it may be associated with an underlying malignancy, most commonly cutaneous Tcell lymphoma. Therapeutic options for alopecia mucinosa are limited. We report a case of alopecia mucinosa successfully treated with minocycline.

B. E. Anderson et al.

Alopecia Mucinosa

FIGURE 1 Patient’s initial presentation.

Case Report A 53-year-old white male presented with a three-year history of a rash predominantly on his forehead, eyelids, and nasal bridge. He was originally diagnosed with Sweets syndrome. For three years he was treated with prednisone of varying doses, which induced a complete remission. Each attempt to taper the prednisone below 5 mg/day caused a relapse of the rash; therefore, he was referred to us for evaluation and treatment. On examination, he had a well-circumscribed red edematous plaque with prominent follicular orifices (Fig. 1). He had no acniform lesions or flushing symptoms. A complete physical exam was done and was normal. Routine blood work, including complete blood count, sedimentation rate, liver function tests, electrolytes and renal function tests, were normal. Antinuclear antibodies were negative. A chest X-ray was normal. A biopsy was performed for H & E and a colloidal iron stain. Histologically there was disruption of the follicular epithelium with intrafollicular deposition of colloidal iron-positive mucin. Within the dermis there was a mixed inflammatory infiltrate composed of lymphocytes, eosinophils, and neutrophils. The histological diagnosis was characteristic for follicular mucinosis (Figs. 2 and 3). The previous biopsies, originally diagnosed as Sweets syndrome, were reevaluated by a dermatopathologist and felt to represent follicular mucinosis. No evidence for cutaneous T-cell lymphoma was seen. The patient was started on minocycline 100 mg po bid. Within 5 weeks the patient had a complete remission and was continued on minocycline 100 mg bid for another 6 weeks. At that time he was decreased to minocycline 50 mg po bid. He has continued on this dose and is still in remission after 7 months of therapy (Fig. 4).

Discussion Clinically, alopecia mucinosa can show multiple morphologies. The classic description is of an erythematous,

125

FIGURE 2 Follicular mucinosis; H E stain, low power.

FIGURE 3 Follicular mucinosis; H E stain, high power.

infiltrated, boggy plaque with prominent follicular orifices and overlying alopecia. These plaques may be solitary or widespread. Typically the plaques occur on the head and neck, but they have been reported to affect all regions of the body. When plaques affect the scalp, eyebrow, or beard area (or other terminal hair-bearing areas), alopecia is prominent. This alopecia is considered a nonscarring alopecia. If vellus hair-bearing skin is affected, the associated alopecia may not be as noticeable. There are many less common presentations for alopecia mucinosa. It may present as morphologically similar to alopecia areata,3 dermatitis,4,5 acneiform eruption,6 pityriasis rosea,7 folliculitis,8 urticaria,9 hypopigmented papules,10 or as a scarring alopecia.11,12 Anesthesia and

126

Journal of Cutaneous Medicine and Surgery

FIGURE 4 Patient after 6 weeks of minocycline therapy.

dysthesia of the plaques as well as exacerbation by light have been reported.13–15 Alopecia mucinosa has been reported to occur along the lines of Blashko.16 The histologic hallmark of alopecia mucinosa is the accumulation of mucin in the follicular epithelium and sebocytes of the affected pilosebaceous apparatus. The histologic appearance is called follicular mucinosis. The mucin is best appreciated with a colloidal iron or alcian blue stain. Occasionally the accumulation of mucin is so massive that there is extensive swelling of the follicular epithelial cells with the loss of intracellular bridges and formation of cystic areas containing enormous quantities of mucin. The mucin is made predominantly of hyaluronic acid, which is an acidic mucopolysaccharide. The source of the mucin in follicular mucinosis is under debate. Some feel the follicular keratinocytes17–19 are the source, while others feel it is a complex interplay of many cell types.20 A nonspecific inflammatory cell infiltrate, predominantly of lymphocytes, is seen in a follicular, perifollicular, and perivascular location.21 Alopecia mucinosa has been shown to be associated with many benign and malignant conditions. It can be seen in childhood but is seen more commonly in adulthood. Alopecia mucinosa is generally felt to occur in three settings: a primary idiopathic form, a form associated with malignancy, and a form secondary to inflammatory conditions.22 The idiopathic form, as seen in this case, is the most common form. This idiopathic group has been split into two subtypes by some authors. Patients in the first subgroup typically have a few scattered edematous plaques on the head and neck, showing follicular prominence.23 These patients tend to have their onset in young adulthood and occasionally childhood. Patients in this first subgroup have a tendency to recover spontaneously.24 In contrast, the other subset of patients with idiopathic alopecia mucinosa have widespread plaques and follicular papules with a relapsing chronic course. The age of onset in this group tends to be in the 4th–6th decades.

Volume 7 Number 2 March 2003

The most commonly associated malignancy seen in conjunction with alopecia mucinosa is cutaneous T-cell lymphoma. One study demonstrated that 32% of the patients with alopecia mucinosa had evidence of cutaneous T-cell lymphoma.25 Although primarily seen in adults in association with alopecia mucinosa, cutaneous T-cell lymphoma can also complicate childhood alopecia mucinosa.26 It may also be seen in patients with the Sezary syndrome.27 The diagnosis of the associated malignancy may precede, coincide, or be made after the diagnosis of alopecia mucinosa. Other associated malignancies that have been documented include Hodgkin’s lymphoma,28–30 chronic lymphocytic leukemia,31,32 acute myelogenous leukemia,33 chronic myelogenous leukemia,17 leukemia cutis,17 Grawitz tumor (clear cell renal carcinoma),34 cutaneous B-cell lymphoma,35 lymphosarcoma,36 squamous cell carcinoma of the tongue,37 and CD30+ cutaneous T-cell lymphoma (Ki 1 lymphoma).38 No uniformly accepted criteria have been used to predict the progression of alopecia mucinosa in those cases that are accompanied by cutaneous T-cell lymphoma or another malignancy. Recently, it has been demonstrated that there are no clear-cut histological criteria to differentiate the idiopathic form of alopecia mucinosa from the lymphoma-associated form.39 Dense lymphoid infiltrates with atypical-appearing lymphocytes can be seen in both idiopathic alopecia mucinosa and lymphoma-associated alopecia mucinosa.39 Thus, we believe that idiopathic alopecia mucinosa may represent a variant of cutaneous T-cell lymphoma, requiring longterm followup to observe for the progression to the classic form of cutaneous T-cell lymphoma.39 Likewise, investigators have tried to develop criteria to determine which cases of alopecia mucinosa would develop into cutaneous T-cell lymphoma, without success.25,31,40 Others have tried to determine if a T-cell clonal expansion was synonymous with lymphoma in cases of alopecia mucinosa. Their results showed that clonal expansion could be seen in lymphoma as well as benign forms of alopecia mucinosa.11,31 The wide range of inflammatory conditions that can be seen in association with the histologic diagnosis of follicular mucinosis include HIV-associated eosinophilic folliculitis,41 angiolymphoid hyperplasia,22 lupus,9,17 leishmaniasis,42 sarcoid,5,17 alopecia areata,43 and familial reticuloendothelosis.44 Hempstead and Ackerman17 reported many associated conditions, including lymphoma, pseudolymphoma, lichen simplex chronicus, acne, nevi, dermatitis, lupus, and arthropod bites. Histologically, follicular mucinosis has also been seen incidentally in nevi45 and lentigo maligna.46 Other rare associations reported include pregnancy47 and Goodpasteur’s syndrome.48 In the inflammatory conditions, follicular mucinosis may represent an incidental histological finding akin to acantholysis. Alopecia mucinosa has been treated with variable success with superficial radiation,1 beta-carotene,15 elec-

B. E. Anderson et al.

Alopecia Mucinosa

tron beam,24 excision,11 X-rays,24 minocycline,6,49 interferon,50 dapsone,4,7 tetracycline,6 isotretinoin,6,51 PUVA,52 indomethacin,53 tretinoin,6,54 topical and intralesional steroids,24,54 oral steroids,2,55,56 methotrexate,24 mepacrine,57 vincristine and cyclophosphamide,28 nitrogen mustard,28 and UVA.58 To our understanding, no placebo-controlled treatment trials for alopecia mucinosa have been published. The treatment of malignancy-associated forms of alopecia mucinosa is directed at the underlying malignancy itself. We chose to use minocycline because of its ease of use, side effect profile, and report of efficacy.49 Yotsumoto et al.49 reported a case of a 36-year-old male with idiopathic follicular mucinosis that responded within two weeks to minocycline with no recurrence. We chose not to continue the patient on oral steroids because of the long-term potential consequences. Minocycline is a semisynthetic tetracycline derivative that has been used to treat many inflammatory conditions.49 Minocycline is not only an antimicrobial agent; it has been shown to inhibit matrix metalloproteinases (e.g., collagenase),59 phospholipase A2,59 polymorphonuclear cell chemotaxis, and nitric oxide production.49 In vitro studies have shown that minocycline has the ability to inhibit epidermal keratinocyte production of TNF-A and increase the production of IL-1A.49,60 Yotsumoto et al.49 proposed the theory that minocycline decreases TNF-A production by inhibiting tissue matrix metalloproteinases, which are required for posttranslational processing of TNF-A.49 There is evidence that cell-mediated immunity plays a role in the pathogenesis of alopecia mucinosa. The mucin deposition is felt to be secondary to the interplay of T cells with the follicular keratinocytes.20 A study showed a majority of the lymphocytes in alopecia mucinosa are of the T-helper-cell lineage. This coupled with the finding of increased Langerhans cells in alopecia mucinosa is the beginning evidence for a possible role for cell-mediated immunity in the pathogenesis of alopecia mucinosa.20 More studies to define the precise role of these inflammatory cells in the pathogenesis of follicular mucinosis are needed. The role of TNF-A and the determination of whether the helper lymphocytes that are present express a Th1 or Th2 profile are two questions that need to be better studied. This research will shed light on the pathogenesis and lead to better and more specific treatments. In conclusion, alopecia mucinosa is a rare dermatosis that can be found in three well-recognized forms: an idiopathic form with two subtypes, a form associated with an underlying malignancy, and a form secondary to inflammatory conditions. Follicular mucinosis can also be incidentally found in biopsy samples. The most common associated malignancy is cutaneous T-cell lymphoma. We report a patient who had an excellent clinical response to prednisone and then to minocycline. Upon diagnosis of alopecia mucinosa, persistent clinical

127

followup is necessary due to the inability to differentiate who is at risk for development of a coexisting underlying malignancy.

References 1. Pinkus H. Alopecia mucinosa: inflammatory plaques with alopecia characterized by root sheath mucinosis. Arch Dermatol 1957; 76:419–424. 2. Dawn G, Handa S, Kumar B. Follicular mucinosis and systemic lupus erythematous. Dermatology 1997; 195:183–184. 3. Snyder R, Crain W, Mc Nutt S. Alopecia mucinosa: Report of a case with diffuse alopecia and normal appearing scalp skin. Arch Dermatol 1984; 120:496–498. 4. Rustin MHA, Bunker CB, Levene GM. Follicular mucinosis presenting as acute dermatitis and response to dapsone. Clin Exp Dermatol 1989; 14:382–384. 5. Zakon SJ, Gendleman M. Alopecia mucinosa. Arch Dermatol 1973; 110:653. 6. Wittenberg GP, Gibson LE, Pittelkow MR, et al. Follicular mucinosis presenting as an acniform eruption: report of four cases. J Am Acad Dermatol 1998; 38:849–851. 7. Kubba R, Stewart T. Follicular mucinosis responding to dapsone. Br J Dermatol 1974; 91:217–220. 8. Johnson WC, Higdon RS, Helwig EB. Alopecia mucinosa. Arch Dermatol 1959; 79:395. 9. Tupker RA, van der Meer JB, Croote AD, et al. Urticaria-like follicular mucinosis in a young female patient. Acta Derm Venereol 1997; 77:323–324. 10. Locker E, Duncan C. Hypopigmentation in alopecia mucinosa. Arch Dermatol 1979; 115:731–733. 11. Jackow CM, Elketra P, Nelson B, et al. Follicular mucinosis associated with scarring alopecia, oligoclonal T-cell receptor VB expansion, and Staphylococcus aureus: When does follicular mucinosis become mycosis fungoides? J Am Acad Dermatol 1997; 36:828– 831. 12. Bonta MD, Tannous ZS, Demierrs M, et al. Rapidly progressing mycosis fungoides presenting as follicular mucinosis. J Am Acad Dermatol 2000; 43:635–640. 13. Matuska MA, Weigand DA. Anesthesia in alopecia mucinosa. Cutis 1987; 40:46–47. 14. Ferreira–Marques J. Sensory imbalance in alopecia mucinosa. Arch Dermatol 1961; 84:170–173. 15. Lagerholm B, Wennersten G. Mucinosis follicularis provoked by light exposure. Acta Derm Venereol 1979; 59:153–156. 16. Tosti A, Fonti PA, Peserico A, et al. Linear alopecia mucinosa along Blaschko’s lines. Acta Derm Venereol 1992; 72:155–156. 17. Hempstead RW, Ackerman AB. Follicular mucinosis: A reaction pattern in follicular epithelium. Am J Dermatopathol 1985; 7(3):245–257. 18. Langer A, Jablonska S, Darynkiewicz Z. Studies on the origin of the mucin in mucinosis follicularis. Acta Derm Venereol 1969; 49:76– 81. 19. Ishibashi A. Histogenesis of mucin in follicular mucinosis. Acta Derm Venereol 1976; 56:163–171. 20. Lancer HA, Bronstein BR, Nakagawa H, et al. Follicular mucinosis: a detailed morphologic and immunopathologic study. J Am Acad Dermatol 1984; 10:760–768. 21. Weedon D. Skin Pathology. New York: Churchill-Livingstone, 1997, pp 347–348. 22. Wolff HH, Kinney J, Ackerman AB. Angiolymphoid hyperplasia with follicular mucinosis. Arch Dermatol 1978; 114:229–232. 23. LeBoit PE, Abel EA, Cleary ML, et al. Clonal rearrangement of the T cell receptor beta gene in the circulating lymphocytes of the erythrodermic follicular mucinosis. Blood 1988; 71(5):1329–1333. 24. Emmerson RW. Follicular mucinosis: a study of 47 patients. Br J Dermatol 1969; 81:395–413. 25. Gibson LE, Muller SA, Leiferman KM, et al. Follicular mucinosis: clinical and histopathologic study. J Am Acad Dermatol 1989; 20:441–446. 26. Schmid MH, Dummer R, Kempf W, et al. Mycosis fungoides with mucinosis follicularis in childhood. Dermatology 1999; 198:284– 287.

128

Journal of Cutaneous Medicine and Surgery

27. Rivers JK, Norris PG, Greaves MW, et al. Follicular mucinosis in association with Sezary syndrome. Clin Exp Dermatol 1987; 12:207–210. 28. Gibson LE, Muller SA, Peters MS. Follicular mucinosis of childhood and adolescence. Pediatr Dermatol 1988; 5(4):231–235. 29. Stewart M, Smoller BR. J Am Acad Dermatol 1991; 24:784–785. 30. Ramon D, Jorda E, Molina I, et al. Follicular mucinosis and Hodgkin’s disease. Int J Dermatol 1992; 31(11):791–792. 31. Mehregan DA, Gibson LE, Muller SA. Follicular mucinosis: Histopathologic review of 33 cases. Mayo Clin Proc 1991; 66:387–390. 32. Thomson J, Cochran REI. Chronic lymphocytic leukemia presenting as atypical rosacea with follicular mucinosis. J Cutan Pathol 1978; 5:81–87. 33. Summer WT, Grichnik JM, Shea CR, et al. Follicular mucinosis as a presenting sign of acute myloblastic leukemia. J Am Acad Dermatol 1998; 39:803–805. 34. Derancourt C, Blanc D, Agache P. Follicular mucinosis associated with a Grawitz tumor. Clin Exp Dermatol 1993; 18(4):391. 35. Benchikhi H, Wechsler J, Rethers L, et al. Cutaneous B-cell lymphoma associated with follicular mucinosis. J Am Acad Dermatol 1995; 33:673–675. 36. Plotnick H, Abbrecht M. Alopecia mucinosa and lymphoma. Arch Dermatol 1965; 92:137–141. 37. Walchmer M, Messer G, Rust A, et al. Follicular mucinosis in association with squamous cell carcinoma of the tongue. J Am Acad Dermatol 1998; 38:622–624. 38. Alagheband M, Cairns ML, Chaung T. Xanthoerythrodermia perstans and alopecia mucinosa in a patient with CD-30 cutaneous T-cell lymphoma. Cutis 1997; 60:41–42. 39. Cerroni L, Fink–Puches R, Back B, et al. Follicular mucinosis. Arch Dermatol 2002; 138:182–189. 40. Nickoloff BJ, Wood C. Benign idiopathic versus mycosis-fungoides-associated follicular mucinosis. Pediatr Dermatol 1985; 2:201– 206. 41. Buezo GF, Fraga J, Abajo P, et al. HIV-associated eosinophilic folliculitis and follicular mucinosis. Dermatol. 1998; 197:178–180. 42. Abajo P, Martin R, Dauden E. Follicular mucinosis associated with cutaneous leishmaniasis. Acta Derm Venereol 1998; 78:315. 43. Fanti PA, Tosti A, Morelli R, et al. Follicular mucinosis in alopecia areata. Am J Dermatopathol 1992; 14(6):542–545.

Volume 7 Number 2 March 2003

44. Freeman RG. Familial reticuloendothelosis with eosinophilia and follicular mucinosis. Arch Dermatol 1972; 105:737–738. 45. Jordaan HF. Follicular mucinosis in association with a melanocytic nevus. A report of 2 cases. J Cutan Pathol 1987; 14:122–126. 46. Nickoloff BJ. Lentigo maligna with follicular mucinosis. Am J Dermatopathol 1985; 7(Suppl):232–233. 47. Roth DE, Owen LG, Hodge SJ, et al. Follicular mucinosis associated with pregnancy. Int J Dermatol 1992; 31:441–442. 48. Jonelis FJ. Simultaneous occurrence of Goodpasteur’s syndrome and follicular mucinosis. Arch Dermatol 1997; 113:1129. 49. Yotsumoto S, Uchimaya H, Kanzaki T. A case of follicular mucinosis treated successfully with minocycline. Br J Dermatol 2000; 142(4):841–842. 50. Meissner K, Weyer U, Kowalzick L, et al. Successful treatment of primary progressive follicular mucinosis with interferons. J Am Acad Dermatol 1991; 24:848–850. 51. Guerriero C, de Simone C, Guidi B, et al. Follicular mucinosis successfully treated with isotretinoin. Eur J Dermatol 1999; 9(1):22–24. 52. Kenicer KJA, Lakshmipathi T. Follicular mucinosis treated with PUVA. Br J Dermatol 1982; 107(22s):48–49. 53. Kodama H, Umemura S, Nohara N. Follicular mucinosis: response to indomethacin. J Dermatol 1988; 15(1):72–75. 54. Fahrner LJ, Solomon AR. Persistent plaques on the face. Pediatr Dermatol 1989; 6(3):254–255. 55. Chadfield HW. Follicular mucinosis (alopecia mucinosa). Br J Dermatol 1965; 77:466–467. 56. Fan J, Chang H, Ma B. Alopecia mucinosa simulating leprosy. Arch Dermatol 1967; 95:354–356. 57. Sonnex TS, Ryan TJ, Dawber RPR. Atypical follicular mucinosis controlled with mepacrine. Br J Dermatol 1981; 105(19 Suppl):83– 84. 58. Von Kobyletzki G, Kreuter JA, Nordmeiser R, et al. Treatment of idiopathic mucinosis follicularis with UVA1 cold light phototherapy. Dermatology 2000; 201(1):76–77. 59. Langevitz P, Livneh A, Bank I, et al. Minocycline in rheumatoid arthritis. Isr J Med Sci 1996; 32:327–330. 60. Celerier P, Litoux P, Dreno B. In vitro modulation of epidermal inflammatory cytokines (IL-1A, IL-6, TNFA) by minocycline. Arch Dermatol Res 1996; 228:411–414.