Acne necrotica (necrotizing lymphocytic folliculitis): An enigmatic and under-recognised dermatosis

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1 Australasian Journal of Dermatology (2018) 59, e53 e58 doi: /ajd SMALL CASE SERIES Acne necrotica (necrotizing lymphocytic folliculitis): An enigmatic and under-recognised dermatosis Lucy K Pitney, 1 Blake O Brien 2 and Michael J Pitney 3 1 Queensland Institute of Dermatology, Greenslopes Hospital, Greenslopes, 2 Sullivan Nicolaides Pathology, and 3 Sherwood Road Dermatology, Brisbane, Queensland, Australia ABSTRACT Acne necrotica is a disorder of adults of obscure aetiology, featuring repeated cropping of inflammatory papulonodules which rapidly necrotise, leaving varying degrees of superficial scarring with pathological features in early lesions of a necrotising lymphocytic folliculitis. A perceived diminishing interest in this entity in recent years prompted a prospective study of patients presenting to a dermatology practice over a 3-year period to reassess the prevalence of this disorder in general dermatological patients, leading to the identification of 47 patients (35 female) with features of acne necrotica, with histopathology undertaken in atypical cases. We identified the importance of the recognition of primary lesions (1 2 mm umbilicated erythematous papules), often difficult to find in excoriated areas, as being paramount in the diagnosis both clinically and histologically in our study, which reveals a significantly more prevalent and clinically diverse disorder than featured in previous textbook and academic journal descriptions. Key words: acne necrotica, dermal hypersensitivity, doxycycline, excoriation, necrotising lymphocytic folliculitis, neurosis, pruritus, urticarial dermatitis. Correspondence: Dr Michael J Pitney, Sherwood Road Dermatology, Level 3, 41 Sherwood Road, Toowong, Brisbane, QLD 4066, Australia. admin@pitneydermatology.com.au Lucy K Pitney, MBBS. Blake O Brien, FRCPA. Michael J Pitney, FACD. Conflict of interest: none. Submitted 28 June 2016; accepted 26 October INTRODUCTION Despite its early recognition as a clinical entity by Bazin in 1851, and the milder miliaris variant in 1928 recognised by Sabauraud, this enigmatic disorder is these days considered rare and its authenticity is doubted by some, 1 rating only a brief mention in major textbooks of dermatology or dermatopathology, and in the Pubmed/Medline database 2016, with a paucity of journal articles 1,2 over recent years. This maybe due in part to the lack of any clear aetiology regarding the disorder 3,4 and a number of impediments to clinical and histological diagnosis that prevent its appropriate recognition. DISCUSSION Acne necrotica is a clinically diverse disorder in which recurring crops of pruritic, painful or tender follicular papulonodules proceed through a number of clinico-pathological stages before resolution, 2,5 with varying degrees of scarring. Pathologically early lesions are characterised by a necrotising lymphocytic folliculitis. 6 To explore the prevalence of acne necrotica among general dermatological patients, a survey was undertaken of patients presenting to a general dermatology practice in Brisbane from 2013 to 2015 inclusive. Altogether 47 patients (35 of whom were women) were identified as having a clinical disorder strongly suggestive of acne necrotica. All patients were adults, with an average age of 55 years (range years). Patients were selected for the study on the basis of cyclically recurring crops of inflammatory papules and nodules, typically in the head and neck region (28), but with a substantial number (19) having atypical features, some with smaller micropapular primary lesions in highly localised areas, others with extremely widespread and heavily excoriated continuously cropping papulonodules. All atypical patients were biopsied, 16 having a confirmatory histology and three with non-specific findings due to suboptimal (late) lesion selection for biopsy. In comparison, 13 patients in total were submitted with a differential diagnosis of acne necrotica by all dermatologists registered with our histopathology provider in the period , with a histological diagnosis of acne necrotica independently offered by the consultant pathologist in seven other

2 e54 LK Pitney et al. cases. This disparity in diagnostic rates led us to believe that there are significant barriers to the appropriate clinical and pathological recognition of acne necrotica. Primary lesions (umbilicated erythematous follicular papules; Fig. 1) are infrequently recognised and seldom biopsied, as either evolving epidermal necrosis or excoriation occur rapidly. 7 Therefore the diagnostic histopathologic features of a superficial perifollicular lymphohistiocytic infiltrate are seldom captured. These are spongiosis and keratinocyte necrosis in the outer root sheath, extending to the adjacent epidermis and dermis, with sub-epidermal oedema 6,8 in pre-necrotic lesions (Fig. 1), followed by superficial crusting overlying evolving confluent necrosis of the upper pilosebaceous unit and adjacent epidermis/dermis with neutrophils in the upper follicular and dermis 7 in early necrotic phase lesions (Fig. 2). Unfortunately, diagnostic areas are only in one or two pathology sections and rapidly cut out. Persistent inflammation and excoriation of established necrotised lesions leads to heavy non-specific perifollicular inflammation (Fig. 3) and occasional foreign body granulomas, 1 masking any remaining pathognomonic features, often leading to erroneous diagnosis. In late lesions non-specific secondary changes both clinical and histological lead to a wide differential diagnosis (Table 1). Although acne necrotica histopathologically is characteristic in its formative phase, 6 significant patience is required in identifying an appropriate lesion for biopsy among the numerous excoriations/necrotised lesions, particularly in the more widespread variants. A number of patient s visits may ensue before an intact early lesion is found. Patients histories are often inconsistent Figure 1 Early pre-necrotic phase lesion/superficial lymphohistiocytic infiltrate, spongiosis and necrosis in outer root sheath extending to adjacent epidermis and dermis with subepidermal oedema. HE 940. Figure 2 Early necrotic phase lesion with superficial follicular crusting, evolving confluent necrosis of upper pilosebaceous unit and adjacent epidermis and dermis. Neutrophils appearing in the upper follicle and dermis. HE 940. Figure 3 Established necrotised lesion with abundant necrosis, excoriation, heavy dermal inflammation. HE 940.

3 Acne necrotica e55 Table 1 Differential diagnosis of acne necrotica Age/sex/prevalence Primary lesions Distribution Course Pathology Treatment Acne necrotica (this series of 47 patients) Adults, average age 55 (Range 21 93). Females (35/47). Considered rare. Acne excoriee Late teens, older adults, usually women. History of acne. Relatively uncommon. Rosacea Young to middle-aged adults. Women predominate Common. Prurigo nodularis Adults, Sexes equal. Younger patients often atopic. Older patients often anxio-neurotic. Folliculitis and Any (depending upon agent). ecthyma Common. Pityriasis lichenoides (PLEVA/PLC) Dermatitis herpetiformis Bite and infestations Children and young adults. Males predominate. Uncommon. All ages. Adults mostly in their 4th decade. Males predominate 2:1. Relatively uncommon. Any age depending on agent. Common. Umbilicated erythematous follicular papulonodules. Dermal hypersensitivity in 7 patients. Naked artefactual excoriations and scarring. Relatively little acne. Telangiectatic persistent erythema and flushing. Superimposed papulopustules. Hyperkeratotic nonfollicular nodules with hyperpigmentation. Follicular pustule/ crusted superficial ulcer. Erythematous papulonodules with parakeratotic superficial scale. PLC: bullous ulceronecrotic lesions. Grouped papulovesicles on erythematous plaques. Intensely pruritic. Firm, non-follicular papules. Occasional bullae (legs) grouped. Secondary infection. Predominantly scalp, head and neck. Less commonly disseminated. Largely face, particularly borders. Occipital scalp and neck. Facial convexities of central face, forehead and chin rhynophyma and lymphoedema. Acral and extensor surfaces. Usually spares face. Hair-bearing areas. Lesions may be solitary, grouped or disseminated. Trunk and proximal limbs spares head and neck. PLC: mucous membranes. Symmetrical over extensor joints. Posterior neck, occipital scalp, natal cleft. Spares face. Mostly exposed areas. Head lice on scalp/neck. Scabies on hands/ genitals. Chronic and cropping. Stress exacerbations. Individual lesions heal over weeks with varioliform scarring or hypopigmentation. Prolonged, leaving artefactual scars. Persistent, gradual worsening with repeated flaring of erythema and papular eruptions. Non-scarring. Individual lesions very chronic. Gradually heal with superficial scarring. Non-cropping. Self-limiting or healing with appropriate antibiotic therapy, good hygiene. Initially persistent with remissions (after 2 years). PLC: crops with varioliform scars. Persistent with periodic flares. Responds to gluten-free diet. Non-scarring. Self-limiting after several days. Occasionally persistent. Scarring uncommon (e.g., ticks). Early: a necrotising lymphocytic folliculitis. Late: heavy, non-specific lymphocytic and polymorph perifollicular inflammation and necrosis. Non-specific features of chronic injury and scarring. Telangiectasia, increased mast cells. Superficial and deep lymphohistiocytic perivascular and periadnexal infiltrate demodex and granulomas. Pseudoepitheliomatous acanthosis, neural and vascular hyperplasia. Spongiosis. Increased mast cells. Dense collection of polymorphs in the pilar duct. Positive bacteriology. Interface dermatitis with necrotic keratinocytes. Extravasated red blood cells, parakeratotic scale. Dense, deep lymphocytic infiltrate. Central nonfollicular. necrosis. Gluten-sensitive enteropathy. Sub-epidermal blister with polymorphs and eosinophils. Positive immunofluorescence for IgA. Superficial and deep perivascular and interstitial lymphocytes and eosinophils spongiosis and vesicle formation. Prominent oedema. Responsive to doxycycline, macrolides and isotretinoin. Unresponsive to topicals. Partial response to antibiotic therapy and isotretinoin. Cognitive behavioural therapy/psychiatry. Responsive to doxycycline, macrolides and isotretinoin. Responds to some topicals (metronidazole, ivermectin). Unresponsive to antibiotic therapy. Intralesional steroids. Phototherapy. Thalidomide, doxepin, azathioprine. Appropriate antibiotic based on culture and sensitivity. Hygiene. Remove potential irritants (e.g., oil). Inconsistent response to doxycycline and macrolide antibiotics. Phototherapy, immunosuppressants. Gluten-free diet. Dapsone. Topical corticosteroids. Nicotinamide. Protective strategies. Anti-scabetics and lice treatment.

4 e56 LK Pitney et al. Table 1 Continued Age/sex/prevalence Primary lesions Distribution Course Pathology Treatment Dermatitis artefacta Adolescence and older. Females 4:1. Uncommon. Drug reactions Potentially any. Mostly adults. Common. Excoriated eczema Infants to adults. Relatively common. Male predominance in atopic dermatitis. Onset 2 6 months of age. Polymorphic, bizarre, linear and angular excoriations and scars. Widespread monomorphic papules or pustules. Non-follicular papulovesicles on a background of excoriated erythema. Macular erythema with crusting and secondary infection. Generally dry skin. Often symmetrical. Face, upper trunk, non-dominant hand/ arm/thigh. Often extensive and symmetrical. Varies with age. Early atopics facial and flexural. Late atopics may be generalised. Contact dermatitis localised or irregular. Always background erythematous dermatitis. Chronic with exacerbations. Chronic: parallels course of drug exposure. Chronic with remissions and exacerbations. 50% atopics remit by mid-teens. Chronic non-specific ulcer. Atrophic/hypertrophic scars. Varies with type of drug. Corticosteroids for infundibular necrosis with perifollicular polymorphs. Often non-distinctive. Spongiosis, intercellular oedema, vesiculation. Lymphohistiocytic infiltrate eosinophils. Raised IgE. Lichenification. Psychotherapy. Cognitive behavioural therapy, antidepressants. Withdraw responsible agents e.g., halogens, hormones, chemotherapy agents and anti-tuberculous agents. Responsive to topical therapies and environmental strategies, allergy management, topical steroids. Short-term response to doxycycline/ macrolides if significant secondary infection or colonisation present. Pityriasis lichenoides chronica, pityriasis lichenoides et varioliformis acuta. Purported infective causes lack any documented evidence. 1

5 Acne necrotica e57 Figure 4 Classical varioliform and miliaris variants. Figure 5 Disseminate and micropapular variants. and confusing, referencing bites, gluten, preservative and food allergy, and often ignore one of the most consistent associations that of anxiety/psychosocial stress, 3 as demonstrated nearly universally in our patients, based on their personal, medical and medication history. Depressive features may complicate diagnosis and treatment. While most patients present with varioliform and miliaris variants (Fig. 4) a high index of suspicion is needed for the clinical diagnosis of many patients presenting with non-classical eruptions, varying from localised and subtle to major and widespread (Fig. 5). We were able to document five distinct patterns of eruptions in our group of patients with acne necrotica (Table 2), all of which responded significantly within weeks to either oral doxycycline 100 mg daily or erythromycin estolate 800 mg b.i.d., presumably due to their anti-inflammatory action. Intermittent treatment was sufficient for mildly affected patients, while some of the more severely affected required constant medication to prevent continuous cropping. An intriguing feature of our patient group was the high incidence of dermal hypersensitivity reaction (urticarial dermatitis large areas of fixed urticarial erythema) which was present in six female and one male patient in the group. CONCLUSION Our study suggests that acne necrotica is significantly under-recognised and contributes a considerable source of chronic patient morbidity, often in emotionally distressed individuals. A high index of suspicion is needed for both clinical and pathological diagnosis as it is almost impossible for the pathologist to make the diagnosis without clinical prompting. Pathology sectioning needs to be done carefully to maximise relevant material so that the

6 e58 LK Pitney et al. Table 2 Clinical variants of acne necrotica case study Distribution Primary lesions Cropping/scarring Excoriation Classical (varioliform) 10 F/8 M Acne necrotica miliaris 3M Head and neck micropapular 11 F/1 M Cape distribution 7F Disseminate 6 F/1 M Scalp, face and neck Scalp and scalp margin Lower face and neck Neck, upper trunk and deltoid Trunk, limbs, often sparing head and neck Large/tumid 5 mm, painful/tender, fewer in number, often grouped Small, 2 mm pustular with burning pruritus Micropapular (1 2 mm) relatively few lesions, sometimes grouped. Bite-like pruritus Extensive and diffuse papules and small nodules (2 5 mm) Extensive papulonodules (2 5 mm) Periodic. Varioliform scars/hypopigmentation. Continuous. Atrophic cribriform scars in hairline. Periodic. Small hypopigmented macules. Continuous. Hypo and hyperpigmented; superficial scarring. Continuous. Hypo and hyperpigmented; superficial scarring. Lesions naturally necrotise. Often too tender to excoriate. Patient may manipulate or squeeze instead. Relatively minor. Patient may rub rather than scratch. Minor; picking individual lesions. Heavily excoriated lesional and non-lesional skin. Heavily excoriated lesional and non-lesional skin. F, female; M, male. pathological features can be more easily identified. We believe our findings should stimulate greater appreciation of the prevalence and clinical and pathological diversity of this intriguing disorder, to the advantage of both physicians and patients. ACKNOWLEDGEMENT The authors gratefully acknowledge the assistance of Dr David Weedon, Order of Australia, whose reporting of our pathology and advice was invaluable. REFERENCES 1. Kligman AM. Necrotizing lymphocytic folliculitis (acne necrotica). In: Plewig G, Kligman Am (eds). Acne and Rosacea, Berlin: Springer, 2000, Milde P, Goertz G. Plewig G [Acne necrotica (varioliformis). Necrotizing lymphocytic folliculitis]. Hautarzt. 1993; 44: Fisher DA. Acne Necroticans (varioliformis) and Staphylococcal Aureus J. Am. Acad. Dermatol. 1988; 1: Maibach HI. Acne necroticans (varioliformis) verses propionibacterium folliculitis. J. Am. Acad. Dermatol. 1989; 21(2 Pt 1): Zirn JR, Scott RA, Hambrick GW. Chronic acneiform eruption with crateriform scars. Acne necrotica (varioliformis) (necrotizing lymphocytic folliculitis). Arch. Dermatol. 1996; 132: Kossard S, Collins A, McCrossin I. Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis). J. Am. Acad. Dermatol. 1987; 16(5 Pt 1): Weedon D. Skin Pathology. Vol.1, 3rd edn. London: Elsevier: Churchill Livingstone, 2010, 15: Ross EK, Shapiro J. Acne necrotica. In: Blume-Peytari U, Whiting DA, Tr ueb RM (eds). Hair Growth and Disorders. Berlin: Springer, 2008;