Dermatology Online Journal

An Unusual Presentation Of A Common Disease
Ioulios Palamaras¹, Peter Kench², Penelope Thomson¹, Abdal Hameed Al-Dulaimi¹, Howard P Stevens¹, Wanda Robles¹
Dermatology Online Journal 14 (3): 4

1. Department of Dermatology, Barnet & Chase Farm NHS Trust, London, UK
2. Department of Histopathology, Barnet & Chase Farm NHS Trust, London, UK

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Abstract

We present a case of perforating granuloma annulare (PGA), in which we show the natural history of lesions and outline the different clinical types. Our patient responded well to intralesional triamcinolone acetonide 10mg/ml injections. Although she was otherwise well, PGA can be associated with diabetes mellitus in up to 17 percent of cases. Differential clinico-histopathological diagnosis, specifically in relation to necrobiosis lipoidica diabeticorum is being discussed. Treatment for PGA is difficult; apart from topical and/or intralesional steroids (clearance up to 54% in one case series), other options include Psoralen plus UVA (PUVA), systemic isotretinoin, chloroquine or hydroxylchloroquine, sulphapyridine, dapsone, topical application of imidazole creams, and liquid nitrogen. Spontaneous remission has also been reported in up to 77 percent in one case series.

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Report of a case

We present the case of a 65-year-old female patient referred to the dermatology department by her general practitioner with a 5-month history of two asymptomatic gradually enlarging papular skin lesions on her left shin.

Figure 1
Figure 1. Presence of two infiltrated yellowish papules on left shin

Physical examination revealed two ill-defined yellowish, infiltrated papules with no perilesional erythema located on her left shin (Fig. 1). Over the next 8 weeks the lesions slowly enlarged, coalesced to form a plaque and ulcerated (Figs. 2 & 3), but remained asymptomatic. The patient was otherwise entirely well and on no topical or systemic medication. Full blood cell count, blood biochemistry, and urinalysis showed no abnormalities.

Figure 2	Figure 3
Figure 2. The papules slowly become nodules, start to ulcerate and coalesce. Figure 3. Formation of an ulcerated plaque with necrotic discharge

A diagnostic punch biopsy specimen was obtained from the left shin (Figs. 4, 5 & 6). Microscopic examination of hematoxylin-eosin-stained sections of the skin biopsy specimen showed a defect in the epidermis through which necrotic material and associated inflammatory cells appeared to be eliminated. The epidermis at one margin of the defect showed regenerative changes. Necrosis of the dermis was largely masked by recent traumatic hemorrhage (Fig. 4). Another section of the biopsy showed the margin of a focus of necrobiosis with numerous attendant histiocytes, some vaguely palisaded (Fig. 5). Smaller foci of necrobiosis could be discerned amongst the histiocytes (Fig. 6). In association with the clinical features, these findings were in keeping with perforating granuloma annulare (PGA).

Figure 4	Figure 5
Figure 4. This section reveals a defect in the epidermis through which necrotic material and associated inflammatory cells appear to be being eliminated. The epidermis at one margin of the defect shows regenerative changes. Necrosis of the dermis is largely masked by recent traumatic hemorrhage. Figure 5. X100 (Initial magnification) Within the dermis are many prominent irregular foci of necrobiosis of collagen adjacent to which are aggregates of histiocytes, some showing a hint of pallisading. NOT SHOWN IN THE SECTIONS: The necrobiosis extends from superficial reticular dermis into subcutis. No giant cells or true vasculitis are detected.

Figure 6
Figure 6. (X200) The section shows the margin of a focus of necrobiosis with numerous attendent histiocytes, some vaguely pallisaded. Smaller foci of necrobiosis can be discerned amongst the histiocytes.

Whilst waiting for the histology results of the diagnostic biopsy, the lesions remained stable (Fig. 3). Initial treatments with topical potent and ultra potent steroid creams (mometasone furoate 0.1%, clobetasol propionate 0.05%) as well as intralesional steroids (triamcinolone acetonide) were helpful. However, the patient subsequently developed three new lesions: on the anterior aspect of the neck, on the right upper arm and the left knee. These were treated successfully with two monthly sessions of intralesional triamcinolone acetonide 10mg/ml. We found that the latter was the most helpful treatment modality for all her lesions - the final result being an atrophic scar. The number of sessions of intralesional injections for resolution of each PGA lesion was 2 to 4 irrespective of its size or duration. The patient was followed-up for a further 8 months. Having achieved clearance of her treated lesions and in the absence of any new lesions, she was then discharged back to her primary care doctor with instructions to return for further assessment if there was any sign of recurrence.

Discussion

Perforating granuloma annulare is a rare subtype of granuloma annulare (GA) named by Owens and Freeman in 1971 [1].

Perforating granuloma annulare tends to appear more frequently in young adults and is more common in women in the first three decades [2]. One review study indicated a prevalence of around 5 percent of GA [2].

Clinically, the lesions pass through four stages: i) erythematous or skin colored papules (similar to Fig. 1), ii) pustular-like lesions that exude thick, creamy, or clear viscous material (Fig. 2), iii) umbilicated or crusted papular-nodular lesions (Fig. 3), and iv) atrophic scars [3]. There are two presentations of PGA: a localized form with lesions mainly in the upper limbs and palms and a more frequently seen, generalized form in the abdominal area, trunk, upper and lower limbs. The generalized form has a chronic course with 37 percent of cases lasting more than 10 years [2].

Perforating granuloma annulare lesions may be solitary in only 9 percent of cases and can be associated with diabetes mellitus in 17 percent of cases [2]. Differential diagnosis includes reactive perforating collagenosis [4], papulonecrotic tuberculid [5], ulcerated rheumatoid nodule [6], perforating sarcoidosis [3], ulcerated or perforating necrobiosis lipoidica diabeticorum (NLD) [7], and, particularly in children, giant molluscum contagiosum [4].

Perforating granuloma annulare is different from GA both histologically and clinically [2]. It seems that the superficial localization of the necrobiotic granuloma in PGA leads to the epidermal perforation and transepidermal and follicular elimination of the necrobiotic material [8].

PGA can be distinguished histologically from necrobiosis lipoidica diabeticorum with features outlined in Table 1 [9, 10]. Some authors consider these to be entities along a continuum.

Treatment of PGA is often unsuccessful. Twelve out of 22 cases (54%) had lesions that resolved following topical, intralesional, or oral steroids. Complete clearing was also achieved in two patients treated with Psoralen plus UVA (PUVA), and in one with oral isotretinoin. Topical application of trichloroacetic acid, imidazole creams, liquid nitrogen, salicylic acid, and oral administration of vitamin A and B6, chloroquine or hydroxylchloroquine, sulphapyridine, dapsone, chlorambucil have been unsuccessful [2]. Spontaneous remission was also reported in 10 of 13 patients (77%) not receiving any treatment [2].

References

1. Owens DW, Freeman RG. Perforating granuloma annulare. Arch Dermatol. 1971 Jan;103(1):64-7 PubMed

2. Penas PF, Jones-Caballero M, Fraga J, Sanchez-Perez J, Garcia-Diez A. Perforating granuloma annulare. Int J Dermatol. 1997 May;36(5):340-8. PubMed

3. Samlaska CP, Sandberg GD, Maggio KL, Sakas EL. Generalized perforating granuloma annulare. J Am Acad Dermatol. 1992 Aug;27(2 Pt 2):319-22. PubMed

4. Woo TY, Rasmussen JE. Disorders of transepidermal elimination. Part 2. Int J Dermatol. 1985 Jul-Aug;24(6):337-48. PubMed

5. Agren-Jonsson S, Holst R, Dahlquist I. Perforating granuloma annulare: report of three cases from Scandinavia. Acta Derm Venereol. 1977;57(6):543-6. PubMed

6. Patterson JW, Demos PT. Superficial ulcerating rheumatoid necrobiosis: a perforating rheumatoid nodule. Cutis. 1985 Oct;36(4):323-5, 328. PubMed

7. Dwyer CM, Dick D, Ulceration in necrobiosis lipoidica--a case report and study. Clin Exp Dermatol. 1993 Jul;18(4):366-9. PubMed

8. Umbert P, Winkelmann RK. Histologic, ultrastructural and histochemical studies of granuloma annulare. Arch Dermatol. 1977 Dec;113(12):1681-6 PubMed

9. Muhlbauer JE. Granuloma annulare. J Am Acad Dermatol. 1980 Sep;3(3):217-30 PubMed

10. Necrobiotic disorders by W.J Cunliffe, chapter 52: p.2297-2309 in Rook's Textbook of Dermatology, WileyBlackwell; 7th Edition, 2004

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