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GRANULOMA ANNULARE IN THE HAND
GRANULOMA ANNULARE IN THE HAND I. GRANT, P. MOHAMMED and P. J. MAHAFFEY From The Lister Hospital, Stevenage, Hertfordshire, UK and The Royal Victoria Infirmary, Newcastle upon Tyne, UK
A review of our cases of granuloma annulare in the hand revealed that it presented as either an annular or subcutaneous lesion, most commonly on the dorsum of the metacarpophalangeal joint of the middle or ring fingers. Lesions were approximately 10 mm in diameter and the diagnosis was confirmed by surgical biopsy. The majority of cases resolved spontaneously within 1 year, and recurrence, though common, did not necessitate a further biopsy. Journal of Hand Surgery (British and European Volume, 2002) 27B: 6: 556–558 patient demographics are summarized in Table 1. The histological findings and clinical history of the seven cases are summarized in Table 2. The typical annular lesion of localized granuloma annulare is shown in Fig. 1 and the characteristic histological findings are shown in Fig 2.
INTRODUCTION Granuloma annulare (GA) is a condition characterized by benign inflammatory skin lesions. The most frequent sites of presentation are the pre-tibial region, the ankle, and the scalp (Felner et al., 1997). Granuloma annulare is a condition commonly diagnosed and managed by dermatologists but can also present as a diagnostic problem in the upper limb. Granuloma annulare is characterized histologically by an area of fibrinoid degeneration of collagen (sometimes referred to as necrobiosis), surrounded by palisading inflammatory cells. Rheumatoid nodules and the cutaneous lesions of necrobiosis lipoidica are also characterized by necrobiosis, and differentiation between these can prove difficult without knowledge of the clinical history and the results of serological testing. We reviewed patients referred to our centre over a 6year period in order to clarify the course and presentation of granuloma annulare in the hand.
RESULTS The patients with granuloma annulare in the hand had a median age of 37 (range, 13–63) years. Five were women and two were men, and all patients were Caucasian. Five of the seven patients had localized granuloma annulare and two had the subcutaneous granuloma annulare subtype. In each case, the disease presented as either one or two painless lesions 7–12 mm in size on the dorsum of the hand. Five of the seven cases involved the ring or middle finger. The most common site of involvement for each digit was the dorsal surface of the metacarpophalangeal joint. It was interesting to note (but of perhaps only anecdotal relevance) that in the case of patient II, there was a family history of granuloma annulare. Her 5-year-old daughter developed GA in the hand at the same time, but was not referred to our unit. No other patient reported any family history of granuloma annulare, and none was diabetic. Four of the seven patients were tested for rheumatoid factor, and none was positive. Patient I suffered from epilepsy and hypertension, for which he had been prescribed carbamezipine and atenolol. Patient III suffered from emphysema and multiple sclerosis. No patient could recall any previous trauma, scarring or occupational injury at the site of the lesion.
PATIENTS AND METHODS A retrospective audit revealed that seven patients with granuloma annulare in the hand had been referred to our centre during the preceding 6 years. The clinical course of the disease in these patients was assessed by examination of the patient’s records, clinical photographs and tissue samples. The patients were telephoned in order to confirm the reported clinical history and to establish if there had been further recurrence. Patients were thus followed up for a period of 2–6 years. The presentation of granuloma annulare in the hand and the Table 1FThe presentation of granuloma annulare in the hand Patient number
Age in years
Sex
Location of lesions
I II III IV V
61 37 63 37 16
Male Female Female Female Female
VI VII
13 54
Female Male
Dorsal surface of metacarpophalangeal joint (MCPJ), left little finger Dorsal surface of MCPJ, right ring finger Dorsal surface of MCPJ, right ring finger Dorsal surface of MCPJ, left middle finger Dorso-ulnar border of proximal interphalangeal joint (PIPJ), right ring finger Dorsal surface of PIPJ, left index finger Dorsal surface of MCPJ, left middle finger
556
Size of lesion (approximate diameter) 7 mm 10 mm 12 mm 7 mm Two lesions, 10 mm in diameter Unknown 8 mm
GRANULOMA ANNULARE
557
Table 2FThe histological findings and clinical history of granuloma annulare in the hand Patient number
Means of diagnosis
I
Excision biopsy
II
GA subtype
Clinical course
Recurrence
Localized
Resolved after 18 months
Incision biopsy
Localized
Resolved after 10 months
III
Incision biopsy
Localized
Resolved after surgery
IV V
Incision biopsy Excision biopsy
Localized Subcutaneous
Resolved after 1 year Lesion wholly excised
VI VII
Incision biopsy Excision biopsy
Subcutaneous Localized
Resolved after 2 years Lesion wholly excised
One episode of recurrence at the same site 1 year later (followed up for 18 months) One episode of recurrence after 1 year at adjacent site Further recurrence within 4 months of surgery, which after 18 months had not resolved No further recurrence during subsequent 6 years Recurrence within 3 months. Spontaneous remission within 1 year, followed 2 years later by further recurrence and remission No further recurrence 1 year after remission No further recurrence 4 years after surgery
Fig 1 The characteristic smooth, annular plaques with indurated borders of localized granuloma annulare.
The disease resolved spontaneously in five of the seven patients, after a median duration of 12 months. In another patient, the granuloma annulare was treated successfully by excision biopsy, and in another (patient III) the disease recurred within 4 months of an excision biopsy and had not resolved after a further 18 months. Recurrence of the disease at the same site, or in the surrounding skin, occurred within 1 year in four of the seven patients. A repeat biopsy was not performed.
DISCUSSION There is no proven aetiology or universally accepted theory of pathogenesis of granuloma annulare (Wells and Smith, 1963). It has four clinically distinct subtypes: localized, generalized, subcutaneous, and perforating. Localized granuloma annulare is by far the most common, and typically presents as multiple, non-scaly, non-pruritic, smooth papules arranged as annular plaques with indurated borders. Localized granuloma
Fig 2 The bright-field micrograph of a biopsy illustrating the typical features of granuloma annulare: there is an area of fibrinoid degeneration of collagen (fdc) surrounded by palisading histiocytes (ph) (Haematoxylin and eosin 400).
annulare tends to present within the first three decades of life and, in the majority of cases, remission occurs spontaneously within a year of presentation (Tan and Goh, 2000). Generalized granuloma annulare is associated with multiple eruptions of small papules, macules, or nodules in annular arrangements. Subcutaneous granuloma annulare presents as a painless soft tissue nodule of the extremities or scalp. These lesions are often referred for surgical opinion and the diagnosis is generally confirmed by biopsy (Grogg and Nascimento, 2001). The lesions resolve spontaneously, but one or more recurrence is common. These do not generally warrant an additional biopsy (Letts et al., 2000). Perforating granuloma annulare is a rare form of the disease characterized clinically by superficial papules on the extremities of children or young adults (Samalaska et al., 1992). These umbilicated lesions develop a yellow central region, which produces a clear viscous mucinous discharge, and subsequently dries to form a crusty scab. Once the condition resolves, there may be an area of hypo- or hyperpigmentation.
558
Granuloma annulare should be considered as a part of the differential diagnosis of an annular lesion on the hand (Hsu et al., 2001). Other potential diagnoses include: tinea corporis, pityriasis rosea, sarcoidosis, and urticaria. Subacute cutaneous lupus erythematosus can also present in an annular form on sun-exposed surfaces. For subcutaneous granuloma annulare, the differential diagnosis should also include rheumatoid nodules. Our study confirms that granuloma annulare in the hand generally occurs on its dorsal surface. The preponderance of women in our study is consistent with the female to male sex ratio of other reported series (Letts et al., 2000). The diagnosis of granuloma annulare was in each case made by excision or incision biopsy. Subcutaneous granuloma annulare can be visualized using magnetic resonance imaging (Chung et al., 1999). However, this investigation is not diagnostic, and can merely be an adjunct to surgical biopsy. Recurrence of the disease does not necessitate a further biopsy and patients can be reassured that the disease in the hand resolves spontaneously in the majority of cases. Previous reports of granuloma annulare in the hand have associated the disease with the sites of persistent trauma or scarring (Beer et al., 1992), and granuloma annulare has also been reported in herpes zoster scars (Ohata et al., 2000). None of the patients in this series reported any previous trauma at the site of their granuloma annulare lesions. An association between granuloma annulare and diabetes mellitus has also been proposed (Studer et al., 1996), but not consistently replicated in other studies. It has been suggested that the onset of granuloma annulare in an adult can be triggered by stressful life events (Studer et al., 1996), or even by the detection of a previously undiagnosed malignancy (Cohen, 1997). In view of the lack of understanding of the pathogenesis of granuloma annulare it is not surprising that there is no clear consensus on the best means of treatment. Shave excision of the lesions, cryotherapy and intra-lesional injection are of unproven benefit and granuloma annulare in the hand usually resolves spontaneously within 1 year, with little or no residual scarring. Recurrence is common within 1 year of resolution of the original lesion but does not warrant
THE JOURNAL OF HAND SURGERY VOL. 27B No. 6 DECEMBER 2002
further biopsy. Once again recurrence tends to be selflimiting. In isolated cases of granuloma annulare that do not resolve, photochemotherapy may have a role. There have been reports of psoralen and ultraviolet A bath photochemotherapy (PUVA) being effective for patients with generalized granuloma annulare (GrundmannKollmann et al., 2000). However, the mainstay of care is the accurate diagnosis of the condition through an initial biopsy, after which the patient can be appropriately reassured. References Beer WE, Wayte DM, Morgan GW (1992). Knobbly granuloma annulare of the fingers – a possible relationship to his work. Clinical and Experimental Dermatology, 17: 63–64. Chung S, Frush DP, Prose NS, Shea CR, Laor A, Bisset GS (1999). Subcutaneous granuloma annulare: MR imaging features in six children and literature review. Radiology, 210: 845–849. Cohen PR (1997). Granuloma annulare associated with malignancy. Southern Medical Journal, 90: 1056–1059. Felner EI, Steinberg JB, Weinberg AG (1997). Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics, 100: 965–967. Grogg KL, Nascimento AG (2001). Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34 cases. Pediatrics, 107: 42–46. Grundmann-Kollmann M, Ochsendorf FR, Zollner TM, Tegeder I, Kaufmann R, Podda M (2000). Cream psoralen plus ultraviolet A therapy for granuloma annulare. British Journal of Dermatology, 144: 996–999. Hsu S, Le EH, Khoshevis MR (2001). Differential diagnosis of annular lesions. American Family Physician, 64: 289–296. Letts M, Carpenter B, Soucy P, Davidson D (2000). Subcutaneous granuloma annulare of the extremities in children. Canadian Journal of Surgery, 43: 425–430. Ohata C, Shirabe H, Takagi K, Kawatsu T (2000). Granuloma annulare in herpes zoster scars. Journal of Dermatology, 27: 166–169. Samalaska CP, Sandberg GD, Maggio KL, Sakas L (1992). Generalized perforating granuloma annulare. Journal of the American Academy of Dermatology, 27: 319–322. Studer EM, Calza AM, Saurat JH (1996). Precipitating factors and associated diseases in granuloma annulare: a retrospective study. Dermatology, 193: 364–368. Tan HH, Goh CL (2000). Granuloma annulare: a review of 41 cases at the National Skin Centre. Annals of the Academy of Medicine, Singapore, 29: 714–718. Wells RS, Smith MA (1963). The natural history of granuloma annulare. British Journal of Dermatology, 75: 199–205.
Received: 28 November 2001 Accepted 21 May 2002 Mr P. J. Mahaffey, Consultant Plastic Surgeon, The Lister Hospital, Stevenage, Hertfordshire SG1 4AB, UK. Tel: +44 1438 314333; Fax: +44 1438 781248 r 2002 The British Society for Surgery of the Hand. Published by Elsevier Science Ltd. All rights reserved. doi: 10.1054/jhsb.2002.0825, available online at http://www.idealibrary.com on
A review of our cases of granuloma annulare in the hand revealed that it presented as either an annular or subcutaneous lesion, most commonly on the dorsum of the metacarpophalangeal joint of the middle or ring fingers. Lesions were approximately 10 mm in diameter and the diagnosis was confirmed by surgical biopsy. The majority of cases resolved spontaneously within 1 year, and recurrence, though common, did not necessitate a further biopsy. Journal of Hand Surgery (British and European Volume, 2002) 27B: 6: 556–558 patient demographics are summarized in Table 1. The histological findings and clinical history of the seven cases are summarized in Table 2. The typical annular lesion of localized granuloma annulare is shown in Fig. 1 and the characteristic histological findings are shown in Fig 2.
INTRODUCTION Granuloma annulare (GA) is a condition characterized by benign inflammatory skin lesions. The most frequent sites of presentation are the pre-tibial region, the ankle, and the scalp (Felner et al., 1997). Granuloma annulare is a condition commonly diagnosed and managed by dermatologists but can also present as a diagnostic problem in the upper limb. Granuloma annulare is characterized histologically by an area of fibrinoid degeneration of collagen (sometimes referred to as necrobiosis), surrounded by palisading inflammatory cells. Rheumatoid nodules and the cutaneous lesions of necrobiosis lipoidica are also characterized by necrobiosis, and differentiation between these can prove difficult without knowledge of the clinical history and the results of serological testing. We reviewed patients referred to our centre over a 6year period in order to clarify the course and presentation of granuloma annulare in the hand.
RESULTS The patients with granuloma annulare in the hand had a median age of 37 (range, 13–63) years. Five were women and two were men, and all patients were Caucasian. Five of the seven patients had localized granuloma annulare and two had the subcutaneous granuloma annulare subtype. In each case, the disease presented as either one or two painless lesions 7–12 mm in size on the dorsum of the hand. Five of the seven cases involved the ring or middle finger. The most common site of involvement for each digit was the dorsal surface of the metacarpophalangeal joint. It was interesting to note (but of perhaps only anecdotal relevance) that in the case of patient II, there was a family history of granuloma annulare. Her 5-year-old daughter developed GA in the hand at the same time, but was not referred to our unit. No other patient reported any family history of granuloma annulare, and none was diabetic. Four of the seven patients were tested for rheumatoid factor, and none was positive. Patient I suffered from epilepsy and hypertension, for which he had been prescribed carbamezipine and atenolol. Patient III suffered from emphysema and multiple sclerosis. No patient could recall any previous trauma, scarring or occupational injury at the site of the lesion.
PATIENTS AND METHODS A retrospective audit revealed that seven patients with granuloma annulare in the hand had been referred to our centre during the preceding 6 years. The clinical course of the disease in these patients was assessed by examination of the patient’s records, clinical photographs and tissue samples. The patients were telephoned in order to confirm the reported clinical history and to establish if there had been further recurrence. Patients were thus followed up for a period of 2–6 years. The presentation of granuloma annulare in the hand and the Table 1FThe presentation of granuloma annulare in the hand Patient number
Age in years
Sex
Location of lesions
I II III IV V
61 37 63 37 16
Male Female Female Female Female
VI VII
13 54
Female Male
Dorsal surface of metacarpophalangeal joint (MCPJ), left little finger Dorsal surface of MCPJ, right ring finger Dorsal surface of MCPJ, right ring finger Dorsal surface of MCPJ, left middle finger Dorso-ulnar border of proximal interphalangeal joint (PIPJ), right ring finger Dorsal surface of PIPJ, left index finger Dorsal surface of MCPJ, left middle finger
556
Size of lesion (approximate diameter) 7 mm 10 mm 12 mm 7 mm Two lesions, 10 mm in diameter Unknown 8 mm
GRANULOMA ANNULARE
557
Table 2FThe histological findings and clinical history of granuloma annulare in the hand Patient number
Means of diagnosis
I
Excision biopsy
II
GA subtype
Clinical course
Recurrence
Localized
Resolved after 18 months
Incision biopsy
Localized
Resolved after 10 months
III
Incision biopsy
Localized
Resolved after surgery
IV V
Incision biopsy Excision biopsy
Localized Subcutaneous
Resolved after 1 year Lesion wholly excised
VI VII
Incision biopsy Excision biopsy
Subcutaneous Localized
Resolved after 2 years Lesion wholly excised
One episode of recurrence at the same site 1 year later (followed up for 18 months) One episode of recurrence after 1 year at adjacent site Further recurrence within 4 months of surgery, which after 18 months had not resolved No further recurrence during subsequent 6 years Recurrence within 3 months. Spontaneous remission within 1 year, followed 2 years later by further recurrence and remission No further recurrence 1 year after remission No further recurrence 4 years after surgery
Fig 1 The characteristic smooth, annular plaques with indurated borders of localized granuloma annulare.
The disease resolved spontaneously in five of the seven patients, after a median duration of 12 months. In another patient, the granuloma annulare was treated successfully by excision biopsy, and in another (patient III) the disease recurred within 4 months of an excision biopsy and had not resolved after a further 18 months. Recurrence of the disease at the same site, or in the surrounding skin, occurred within 1 year in four of the seven patients. A repeat biopsy was not performed.
DISCUSSION There is no proven aetiology or universally accepted theory of pathogenesis of granuloma annulare (Wells and Smith, 1963). It has four clinically distinct subtypes: localized, generalized, subcutaneous, and perforating. Localized granuloma annulare is by far the most common, and typically presents as multiple, non-scaly, non-pruritic, smooth papules arranged as annular plaques with indurated borders. Localized granuloma
Fig 2 The bright-field micrograph of a biopsy illustrating the typical features of granuloma annulare: there is an area of fibrinoid degeneration of collagen (fdc) surrounded by palisading histiocytes (ph) (Haematoxylin and eosin 400).
annulare tends to present within the first three decades of life and, in the majority of cases, remission occurs spontaneously within a year of presentation (Tan and Goh, 2000). Generalized granuloma annulare is associated with multiple eruptions of small papules, macules, or nodules in annular arrangements. Subcutaneous granuloma annulare presents as a painless soft tissue nodule of the extremities or scalp. These lesions are often referred for surgical opinion and the diagnosis is generally confirmed by biopsy (Grogg and Nascimento, 2001). The lesions resolve spontaneously, but one or more recurrence is common. These do not generally warrant an additional biopsy (Letts et al., 2000). Perforating granuloma annulare is a rare form of the disease characterized clinically by superficial papules on the extremities of children or young adults (Samalaska et al., 1992). These umbilicated lesions develop a yellow central region, which produces a clear viscous mucinous discharge, and subsequently dries to form a crusty scab. Once the condition resolves, there may be an area of hypo- or hyperpigmentation.
558
Granuloma annulare should be considered as a part of the differential diagnosis of an annular lesion on the hand (Hsu et al., 2001). Other potential diagnoses include: tinea corporis, pityriasis rosea, sarcoidosis, and urticaria. Subacute cutaneous lupus erythematosus can also present in an annular form on sun-exposed surfaces. For subcutaneous granuloma annulare, the differential diagnosis should also include rheumatoid nodules. Our study confirms that granuloma annulare in the hand generally occurs on its dorsal surface. The preponderance of women in our study is consistent with the female to male sex ratio of other reported series (Letts et al., 2000). The diagnosis of granuloma annulare was in each case made by excision or incision biopsy. Subcutaneous granuloma annulare can be visualized using magnetic resonance imaging (Chung et al., 1999). However, this investigation is not diagnostic, and can merely be an adjunct to surgical biopsy. Recurrence of the disease does not necessitate a further biopsy and patients can be reassured that the disease in the hand resolves spontaneously in the majority of cases. Previous reports of granuloma annulare in the hand have associated the disease with the sites of persistent trauma or scarring (Beer et al., 1992), and granuloma annulare has also been reported in herpes zoster scars (Ohata et al., 2000). None of the patients in this series reported any previous trauma at the site of their granuloma annulare lesions. An association between granuloma annulare and diabetes mellitus has also been proposed (Studer et al., 1996), but not consistently replicated in other studies. It has been suggested that the onset of granuloma annulare in an adult can be triggered by stressful life events (Studer et al., 1996), or even by the detection of a previously undiagnosed malignancy (Cohen, 1997). In view of the lack of understanding of the pathogenesis of granuloma annulare it is not surprising that there is no clear consensus on the best means of treatment. Shave excision of the lesions, cryotherapy and intra-lesional injection are of unproven benefit and granuloma annulare in the hand usually resolves spontaneously within 1 year, with little or no residual scarring. Recurrence is common within 1 year of resolution of the original lesion but does not warrant
THE JOURNAL OF HAND SURGERY VOL. 27B No. 6 DECEMBER 2002
further biopsy. Once again recurrence tends to be selflimiting. In isolated cases of granuloma annulare that do not resolve, photochemotherapy may have a role. There have been reports of psoralen and ultraviolet A bath photochemotherapy (PUVA) being effective for patients with generalized granuloma annulare (GrundmannKollmann et al., 2000). However, the mainstay of care is the accurate diagnosis of the condition through an initial biopsy, after which the patient can be appropriately reassured. References Beer WE, Wayte DM, Morgan GW (1992). Knobbly granuloma annulare of the fingers – a possible relationship to his work. Clinical and Experimental Dermatology, 17: 63–64. Chung S, Frush DP, Prose NS, Shea CR, Laor A, Bisset GS (1999). Subcutaneous granuloma annulare: MR imaging features in six children and literature review. Radiology, 210: 845–849. Cohen PR (1997). Granuloma annulare associated with malignancy. Southern Medical Journal, 90: 1056–1059. Felner EI, Steinberg JB, Weinberg AG (1997). Subcutaneous granuloma annulare: a review of 47 cases. Pediatrics, 100: 965–967. Grogg KL, Nascimento AG (2001). Subcutaneous granuloma annulare in childhood: clinicopathologic features in 34 cases. Pediatrics, 107: 42–46. Grundmann-Kollmann M, Ochsendorf FR, Zollner TM, Tegeder I, Kaufmann R, Podda M (2000). Cream psoralen plus ultraviolet A therapy for granuloma annulare. British Journal of Dermatology, 144: 996–999. Hsu S, Le EH, Khoshevis MR (2001). Differential diagnosis of annular lesions. American Family Physician, 64: 289–296. Letts M, Carpenter B, Soucy P, Davidson D (2000). Subcutaneous granuloma annulare of the extremities in children. Canadian Journal of Surgery, 43: 425–430. Ohata C, Shirabe H, Takagi K, Kawatsu T (2000). Granuloma annulare in herpes zoster scars. Journal of Dermatology, 27: 166–169. Samalaska CP, Sandberg GD, Maggio KL, Sakas L (1992). Generalized perforating granuloma annulare. Journal of the American Academy of Dermatology, 27: 319–322. Studer EM, Calza AM, Saurat JH (1996). Precipitating factors and associated diseases in granuloma annulare: a retrospective study. Dermatology, 193: 364–368. Tan HH, Goh CL (2000). Granuloma annulare: a review of 41 cases at the National Skin Centre. Annals of the Academy of Medicine, Singapore, 29: 714–718. Wells RS, Smith MA (1963). The natural history of granuloma annulare. British Journal of Dermatology, 75: 199–205.
Received: 28 November 2001 Accepted 21 May 2002 Mr P. J. Mahaffey, Consultant Plastic Surgeon, The Lister Hospital, Stevenage, Hertfordshire SG1 4AB, UK. Tel: +44 1438 314333; Fax: +44 1438 781248 r 2002 The British Society for Surgery of the Hand. Published by Elsevier Science Ltd. All rights reserved. doi: 10.1054/jhsb.2002.0825, available online at http://www.idealibrary.com on