Perforating Granuloma Annulare Research Articles

Generalized perforating granuloma annulare appearing during pregnancy

Dear Editors, Granuloma annulare (GA) is a benign granulomatous dermatosis with a prevalence of 0.1% to 0.4%. Generalized perforating GA is an extremely rare variant.1 We report a case of a 20-year-old G2P1 (T1-P0-A0-L1) who presented with multiple pruritic papules on the legs and trunk during her first trimester, with no systemic symptoms. She was not on any medication and has no known illnesses, with no similar symptoms during her first pregnancy. On her 37th week age of gestation, the lesions developed central punctum and overlying vesicles and pustules (Fig. 1A–C). Differential diagnoses at this time were papular urticaria, pemphigoid gestationis, and polymorphic eruption of pregnancy. On day 6 postpartum, her lesions evolved into violaceous papules and plaques, some ulcerated with discharge and tenderness (Fig. 1D–F). At this time, generalized pyoderma gangrenosum was considered. Wound gram stain and culture showed negative results. Complete blood count, urinalysis, liver function, and fasting blood sugar were normal. On day 20 postpartum, an incisional wedge biopsy was done on the lesion in Figure 1F, revealing findings consistent with perforating GA (Fig. 2).Fig. 1.: (A–C) On the 37th week age of gestation, multiple erythematous papules and plaques developed, some with central punctum as well as overlying vesicles and pustules; (D–F) on day 6 postpartum, multiple erythematous to hyperpigmented papules and nodules developed on the torso and extremities, some perforated, with an ulcerated plaque with yellowish discharge and black crusts on the right lower leg; (G, H) On day 49 postpartum, after 2 wk on topical steroids, further flattening of lesions and healing of perforated areas were noted.Fig. 2.: (A–C) The incisional wedge biopsy revealed parakeratosis, moderate spongiosis with pseudoepitheliomatous hyperplasia and areas of focal ulceration and follicular involvement, palisading granulomas around small foci of mild connective tissue degeneration with mucin accumulation, superficial and deep moderate infiltrates of lymphocytes, neutrophils, eosinophils, and plasma cells, as well as deep dermal scarring; (D) Alcian blue stain confirmed the presence of mucin.On day 35 postpartum, the patient noted improvement and resolution of pain even without treatment. She was prescribed clobetasol propionate ointment twice daily for 2 weeks, after which she reported further improvement and healing of perforated areas (Fig. 1G, H). At 3 months postpartum, continuous improvement with no recurrence was noted. Generalized perforating GA is rarely reported in literature. It is seen in patients aged 1 to 60 years, predominantly females.1 The etiology of GA is unclear, although it is hypothesized to be an immune reaction of the body inciting a proinflammatory state leading to tissue destruction.2 Although majority of cases are idiopathic, triggers have been reported for generalized perforating GA, including insect bites, ultraviolet radiation, trauma, thyroiditis, and diabetes mellitus.1 In our patient, there were no apparent triggers or associated illnesses based on a thorough history and laboratory tests. It is noteworthy that she was pregnant when her lesions appeared, and improvement even without treatment occurred at about 1 month postpartum. To our knowledge, there are no studies in literature demonstrating an association between GA and pregnancy. One study reported a pregnant patient with GA whose lesions resolved at the fifth month of pregnancy, but returned at 6 months postpartum and persisted for 6 years. Another patient in this study noted recurrence of lesions during pregnancy, but resolution after 3 months while still pregnant.3 During pregnancy, the immune system undergoes complex changes that alters one’s inflammatory response. Particularly, the first and last trimesters are characterized as proinflammatory states, with high levels of T-helper 1 cells and its associated cytokines.4 Although the etiology of GA is not fully elucidated, several studies support a delayed Th1 immune response, with Th1-associated cytokines inducing inflammation and subsequent tissue destruction in the skin, as evidenced by the characteristic symptoms and histopathology in GA.2 These similarities in the immunologic profiles of both pregnancy and GA have led us to hypothesize that immune system changes during pregnancy may have contributed or possibly triggered GA in our patient, especially considering that generalized GA responds poorly to treatment,5 but her lesions improved postpartum even without intervention. Although no established association exists, pregnancy is a condition that warrants further investigation as a possible triggering or associated condition in GA, as our patient’s lesions coincided with pregnancy and resolved postpartum. Conflicts of Interest None. Declaration of patient consent: Informed, written consent was received from all patients and confirmed to the journal pre-publication, stating that the patients gave consent for their photos and case history to be published. Funding None. Study Approval N/A.

Malignancy-Associated Generalized Granuloma Annulare in a Japanese Patient with Stomach Cancer and Diabetes Mellitus

Granuloma annulare is a benign granulomatous dermatosis with variable clinical presentation. It is of unknown origin and results in erythematous, brown, or skin-colored annular plaques usually found over boney surfaces on the extremities. The main variants are localized granuloma annulare, subcutaneous granuloma annulare, perforating granuloma annulare, and generalized granuloma annulare. Systemic diseases proposed to have an association with granuloma annulare include diabetes mellitus, dyslipidemia, hypothyroidism, and various malignancies. Cohen [1] coined the term ‘malignancy-associated granuloma annulare’ to describe a form of granuloma annulare that is temporally associated with a malignant process, in which the onset of granuloma annulare coincides with the discovery of a previously unsuspected neoplasm or metastatic disease, and the course of the granuloma annulare also parallels that of the tumor. We present a Japanese patient with malignancy-associated generalized granuloma annulare as the first manifestation of stomach cancer based on diabetes mellitus.

Retraction: “Perforating Granuloma Annulare Appearing as a Psoriasiform Lesion”

Retraction: “Perforating Granuloma Annulare Appearing as a Psoriasiform Lesion”

Generalized perforating granuloma annulare: a case report

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Perforating Granuloma Annulare Mimicking Psoriasis

Perforating granuloma annulare (PGA) is a rare inflammatory condition characterized by transepithelial elimination of necrobiotic collagen with granulomas in the dermis. It commonly presents as umbilicated papules or pustules on the extremities and dorsal hands. The distribution of PGA can be described as generalized or localized, with only 9% of patients presenting with a single lesion. Herein, we report an unusual presentation of PGA as a single localized plaque on the forearm that resembled psoriasis.

Perforating granuloma annulare in children: A case report

Perforating granuloma annulare in children: A case report

Perforating granuloma annulare in a young male following application of the tattoo.

Perforating granuloma annulare in a young male following application of the tattoo.

Perforating granuloma annulare mimicking papulonecrotic tuberculid

A case is reported of a patient presenting lymph node tuberculosis and cutaneous lesions resembling papulonecrotic tuberculid, but histologically compatible with perforating granuloma annulare and which responded satisfactorily to antituberculous therapy. This is probably one of the first reports of the association of perforating granuloma annulare and tuberculosis, and it is important therefore to highlight the relevance of this disorder in the differential diagnosis of papulonecrotic tuberculid and to raise the hypothesis that this entity should also be considered to be a variant of tuberculid.

Perforating Granulomatous Dermatitis Reaction to Exogenous Tattoo Pigment

: The majority of cutaneous hypersensitivity reactions to exogenous tattoo pigments can be histologically classified as lichenoid or granulomatous. The etiology is still uncertain but is generally accepted to be a delayed-type hypersensitivity reaction to either the pigment itself or its carrier solution. In this report, we review the literature concerning adverse reactions to tattoos. In addition, we describe the second case of a localized granulomatous dermatitis to the red dye within a tattoo that histologically resembled granuloma annulare. This is the first reported example of a perforating granuloma annulare-like reaction.

Granuloma Annulare

Granuloma annulare is a benign, usually self-limited granulomatous disease of the dermis and subcutaneous tissue. Several distinct subtypes have been recognized, namely localized granuloma annulare, generalized or disseminated granuloma annulare, subcutaneous granuloma annulare, papular granuloma annulare, interstitial or patch granuloma annulare, and perforating granuloma annulare. Localized granuloma annulare is the most common form in children and comprises 75% of cases. Clinically, the condition is characterized by asymptomatic, flesh-colored or erythematous-brown papules, frequently arranged in a ring or annular pattern on the distal extremities. It is estimated that 0.1 to 0.4% of new patients attending dermatologic clinics have granuloma annulare. Most cases of granuloma annulare occur before the age of 30 years. A delayed hypersensitivity and cell-mediated immune response to an antigen contributes to the pathogenesis. Histologic examination of the lesion shows central collagen degeneration and mucin deposition surrounded peripherally by palisading histiocytes and inflammatory cells. Most cases of granuloma annulare are asymptomatic and self-limited; and reassurance is often sufficient. Treatment is mainly for cosmetic purposes and various modalities of treatment options are discussed.

Granuloma anular perfurante generalizado

The authors present a clinicopathological case of Generalized Perforating Granuloma Annulare with extensive distribution of lesions, which are shown in various stages of development. Pustules, papular lesions in annular and arcuate distribution, erosions covered with hematic crusts, maculopapular atrophic areas and scars were the presentation forms of the disease. The histopathological aspects are discussed in detail within non-infectious granulomatous dermatitis. The text is based on the opinions of some authors in the literature. Furthermore, the therapeutic result obtained after three months of Dapsone at a dose of 100 mg per day was demonstrated by photographs.

Granulome annulaire perforant unique avec phénomène d’élimination transfolliculaire

The perforating granuloma annulare is a rare form of granuloma annulare. The clinical diagnosis is difficult and the confirmation is histological. The localisation is unique in less than 10% of all cases. We report a documented case with a histological suspicion of transfollicular perforation. A 36 year-old woman, without any particular antecedent, presented on her upper arm a single ulcerated nodular lesion that had evolved for one year. The clinical examination and biological investigations were normal. The histological examination led to the diagnosis of perforating granuloma annulare with a large epidermic ulceration. Treatment with a topical corticosteroid was disappointing and the removal was decided. In our observation, the single localization of this lesion raises the problem of differential diagnosis such as cutaneous tuberculosis, atypical mycobacteriosis, skin sarcoidosis, foreign body granuloma, epidermoid carcinoma or perforating dermatitis. The histological examination permitted diagnosis of a perforating granuloma annulare with large epidermic ulceration. The infiltration and destruction of a hair follicle evoked the possible transfollicular elimination of the necrotic material. Other pathologies with the histological aspect of a palisading granuloma were excluded from this context. No associated pathology such as diabetes nor any other favouring factors such as ultraviolet light or insect bites or traumas were identified. The physiopathology of perforating granuloma annulare and the process of perforation remain unknown. Numerous therapies have been proposed with variable results.

Expression of the 67-kDa elastin receptor in perforating skin disorders.

Perforating skin dermatoses include elastosis perforans serpiginosa (EPS), reactive perforating collagenosis, Kyrle's disease and perforating folliculitis. In addition to these four diseases, an acquired form of perforating dermatosis associated with diabetes mellitus and/or chronic renal failure has been reported for which the term acquired perforating dermatosis (APD) was proposed. The molecular mechanism of transepidermal elimination of dermal components in perforating skin dermatoses remains unclear. We recently demonstrated that the 67-kDa elastin receptor can be detected in the epidermis eliminating altered elastic fibres in EPS, suggesting that the elastin-keratinocyte interaction may play a role in transepidermal elimination in EPS. To determine whether the 67-kDa elastin receptor is involved in other perforating diseases. Paraffin-embedded skin specimens from new cases of EPS (n = 2), APD (n = 15) and perforating granuloma annulare (PGA; n = 2) were studied immunohistochemically using a specific antibody to the 67-kDa elastin receptor. In one case of EPS, two different sites from a single lesion, a central atrophic area and a peripheral keratotic area, were studied. Expression of the elastin receptor was detected in the epidermis surrounding the elastic materials in both cases of EPS. The elastin receptor was not detected in the central inactive area, whereas it was expressed strongly in the peripheral keratotic active area. The elastin receptor was also detected in three of 15 cases of APD in which a few elastic fibres were found in the eliminated dermal materials. In one case of APD, the elastin receptor was not detected in spite of the presence of a few elastic fibres in the eliminated materials. The elastin receptor was not detected in either case of PGA. Expression of the elastin receptor in EPS was seen in both cases studied and was dependent on the stage of the lesion. Expression of the elastin receptor in APD appeared to be related to the amount of elastic fibres in the eliminated materials. Thus, expression of the elastin receptor in perforating skin disorders may depend on the stage of the lesion and/or the content of elastic fibres in the dermal materials being eliminated.

Patch granuloma annulare: Clinicopathologic study of 6 patients

Background: Granuloma annulare is a common skin disorder that usually presents with smooth papules arranged as annular plaques. Variants, such as disseminated, subcutaneous, and perforating granuloma annulare, have been described. Objective: The purpose of this study is to describe the clinical and histologic features of a distinct patch form of granuloma annulare. Methods: The clinical and histologic features of 6 patients with patch granuloma annulare were evaluated. Results: Six women 27 to 72 years of age had patches on the extremities. Two patients also had a lesion on the trunk. Only one patient had annular patches. Histologic examination showed an interstitial infiltrate of lymphocytes and histiocytes with diffuse necrobiosis. Conclusion: Patch granuloma annulare is a distinct variant with rather subtle clinical and histologic features. A high index of suspicion both clinically and histologically aids in making the diagnosis. (J Am Acad Dermatol 2000;42:417-21.)

Association of subcutaneous and perforating granuloma annulare with primary sclerotic cholangitis

Association of subcutaneous and perforating granuloma annulare with primary sclerotic cholangitis

Systemic Scleroderma and Perforating Granuloma annulare: Differential Diagnosis from Calcinosis

Systemic scleroderma is a disorder of unknown etiology with skin sclerosis. Its major histological features are swollen and homogenized collagen bundles. We describe 2 patients with systemic sclerosis who have multiple umbilicated nodules indistinguishable from calcinosis cutis. Histological examinations including Von Kossa staining revealed features of perforating granuloma annulare, but not of calcinosis cutis. The association may not be fortuitous but both diseases may be etiologically related.

A Case of Disseminated Perforating Granuloma Annulare in a Child

A Case of Disseminated Perforating Granuloma Annulare in a Child

Perforating granuloma annulare: Response to treatment with isotretinoin

A 21-year-old woman had a painful eruption on the hands, elbows, and knees. She reported the occasional spontaneous discharge of viscous fluid, followed by crusting. Response to treatment with potent topical steroids had been poor. Examination revealed numerous 2 to 8 mm umbilicated papules (Fig. 1); many of the lesions had coalesced and others were ulcerated. A punch biopsy of a papule from the hands demonstrated transepidermal elimination of degenerate mutinous collagen bundles, and granulomas with palisading lymphoid cells and histiocytes. For 2 years the patient was treated with topical 0.05% clobetasol propionate under occlusion, repeated intralesional injections with triamcinolone, and cryotherapy with poor response. A trial of isotretinoin (0.75 mg/kg/ day) was begun because of recent reports of the successful use of retinoids in classic granuloma annulare (GA) .l, 2 Near-complete resolution of the papulcs was seen within 10 weeks with dramatic relief of pain (Fig. 2). Cessation of treatment resulted in recurrence of some lesions during a 6-month period. Treatment with isotretinoin (0.5 mg/kg/day) was begun with satisfactory control of the disease and fewer side effects. Treatment was stopped after 4 months because of the patient’s desire to become pregnant. Although a few lesions have persisted, no relapse has been observed 6 months later.

Papulonecrotic Tuberculid

We report 10 women and five men with papulonecrotic tuberculid, an uncommon form of cutaneous tuberculosis (TB). The mean age was 22.6 years (range, 2 1/2-35 years) at presentation. The Mantoux test was strongly positive in 13 patients. Five patients showed presumptive evidence of associated TB; in one case, the presence of TB was proven by culture. Response to anti-TB was dramatic in all cases. Clinical findings were similar to those previously published. We emphasize the simultaneous occurrence of erythema induratum, associated Takayasu's disease, possible associated phlebitic tuberculid, and clinical mimicry of acute bacterial endocarditis. The main histopathological findings obtained from 27 biopsy specimens included dermal necrosis (26 of 27 cases), a poorly formed granulomatous infiltrate (27 of 27 cases), vasculitis (11 of 27 cases), perivascular spongy edema (11 of 27 cases), and follicular necrosis or suppuration (five of 27 cases). A Ziehl-Neelsen stain was negative in all biopsy specimens. Immunohistochemical labeling revealed a preponderance of T-lymphocytes (UCHL-1+), monocytes-macrophages (S-100+), and Langerhans cells (ACT+), indicative of a type IV hypersensitivity reaction. B-lymphocytes (L26+) were sparse. Conditions that may be confused with PNT on clinical or histopathological ground include pityriasis lichenoides et varioliformis acuta, papular urticaria, papulopustular syphilide, miliary TB, septicemia, perforating granuloma annulare, chondrodermatitis nodularis, reactive perforating collagenosis, allergic granulomatosis, suppurative folliculitis, and infectious causes of palisading granulomas. Papulonecrotic tuberculid has distinct clinical, histopathological, and immunohistochemical features. Awareness of this entity is important since an appropriate diagnosis is necessary for the institution of timely curative treatment.

Generalized perforating granuloma annulare

Generalized perforating granuloma annulare is characterized by 1 to 4 mm umbilicated papules on the extremities, and is most commonly seen in children and young adults. Trans-epithelial elimination of mucinous, degenerating collagen fibers and surrounding palisading lymphohistiocytic granulomas are important histologic features. Perforating sarcoidosis and perforating granuloma annulare may be difficult to differentiate because of a similar clinical appearance and the presence of sarcoidal granulomas in biopsy specimens. A particularly high incidence of perforating granuloma annulare has been reported in the Hawaiian Islands.