British Journal of Dermatology (1975) 93, 85.
Granuloma annulare and necrobiosis lipoidica treated by jet injector G.SPARROW AND E.ABELL St John's Hospital for Diseases of the Skin, London W.C.2 Accepted for publication 25 October 1974
SUMMARY
A Porto-jet injector was employed to treat forty-five cases of granuloma annulare and five cases of necrobiosis lipoidica with triamcinolone acetonide or sterile normal saline. Complete clearance of granuloma annulare lesions was achieved in nearly 70",, of those receiving triamcinolone and in 44% with saline. Inadequate penetration of lesions was responsible for a number of failures. The rate of recurrence after treatment was high but retreatment was usually successful. In three cases of necrobiosis lipoidica complete resolution occurred, while in one, partial improvement was obtained. No serious complications of this type of treatment were observed.
Granuloma annulare (G.A.) is a benign condition which frequently presents a therapeutic problem. It runs a variable course before ultimate spontaneous resolution but this course is often very protracted. In a series of 115 cases (Wells & Smith, 1963), only half resolved within 2 years, while the overall duration varied from 3 months to 25 years. In addition, even after spontaneous clearance, 41" „ of their patients had one or more recurrences, which although usually resolving more quickly than the primary lesion were, none the less, persistent. Many methods of treatment have been advocated but little information appears to exist about their effectiveness. Intra-lesional injection has been employed, and in a small series reported by Kern & Schiff (i960) it was suggested that hydrocortisone, saline, sterile water, procaine and xylocaine could be used equally successfully. Necrobiosis lipoidica (N.B.L.), whether associated with diabetes or not, also undergoes spontaneous healing, but very infrequently (Rollins & Winkelmann, i960). Topical corticosteroids (Savitt, 1955; Newman & Feldman, 1951) and surgical excision and grafting (Nylen & Skoog, 1958) have been advocated as treatment. Injections of hydrocortisone have also been used with success in four patients reported by Marten & Dulake (1957), using conventional methods. This study details the results obtained after the treatment of a large series of patients with G.A., using a Porto-jet needleless injector. An attempt has been made to assess both the effect of saline and triamcinolone acetonide and also the frequency of recurrence following clearance induced by treatment. Five cases of N.B.L. are also included. 85
G.Sparrow and E.Abell
86
MATERIALS AND METHODS
Forty-five patients with G.A. and five with N.B.L. were treated. They ranged in age from 8 to 73 years and consisted of 35 females and 15 males. In twenty-seven, the diagnosis was confirmed by biopsy. One patient with G.A. and two with N.B.L. were diabetic, while eight patients with G.A. gave a family history of diabetes. The mean duration of the G.A. was 3 years (range 5 months to 15 years); only six patients were recorded to have had previous spontaneous clearance. Two of the cases of N.B.L. had atypical annular necrobiosis of the face (Wilson Jones, 1971), confirmed by biopsy. One of these had a combination of annular lesions on die back and face, with typical necrobiosis lipoidica on the shins. The other had G.A.-like lesions on the elbows. In none of the cases of N.B.L. had the condition progressed to severe atrophy or ulceration. Injections of 01 ml triamcinolone acetonide (5 mg/ml) or of sterile normal saline were delivered into the G.A. lesions to produce even infiltration. The plaques of N.B.L. were infiltrated around the active margins before the central areas were treated. Great care was taken to avoid injecting areas of marked atrophy. Injections were performed with a Porto-jet needleless injector as described previously (Verbov & Abell, 1970). Initially patients were treated with a series of three injections at 2weekly intervals, but this was subsequently modified as single injections gave similar results on followup. Subsequently injection given at 6- to 8-weekly intervals were performed as indicated by the clinical situation. The number of treatments varied from i to 16 (mean 2-4) and the follow up period from 2 months to 2 years (mean 4-5 months). For assessment purposes, results were grouped as follows: (a) Complete clearance of all treated lesions. (b) Partial clearance. (c) No change. Five cases in which initial partial improvement was followed by rapid relapse were assessed as being unchanged. Twenty-six and twenty-five patients with the nodular form of G.A. received sterile normal saline and triamcinolone acetonide respectively. Eleven patients in each group received both types of therapy for separate lesions. Five patients with diffuse G.A. and the five with N.B.L. were treated with triamcinolone acetonide. TABLE I. Injection treatment of granuloma annulare Results Cases
Mean no. treatments
Mean no. injections
Complete clearance
Partial clearance
No change
Recurred
Triamcinolone acetorade
Nodular Diffuse
25
29
32 S4
17(68%) 6(24%) 3 1 1
2(8%) -
8(47%)
1-6 I
34 18
12 (44%) 9 (33%)
6 (22%)
5
5
Normal saline
Nodular Diffuse
27 I
RESULTS
Complete clearance of G.A. lesions was achieved in 17 of 25 (68",,) treated with triamcinolone (Figs. I and 2) and in 12 of 27 (44%) using sterile saline; in both groups the recurrence rate was high, being
Granidoma annulare and necrobiosis lipotdica treated by jet injector
FIGURE I. Granuloma annulare before treatmeni.
FIGURE 2. Granuloma annulare 5 months after treatment (triamcinolone acetonide).
8 and 5 respectively. Resolution usually took 2-4 weeks after successful injection and recurrences appeared within 3-7 months of the time of initial treatment. Thirteen of these patients with recurrent lesions were retreated, only one of whom failed to respond. Certain patterns of response appeared during the follow-up. Over half the patients responded by rapid and complete clearance with a small number of injections (1-3). In a small group improvement occurred in the sites injected coincidental with the development of new lesions elsewhere. This led to prolonged periods of treatment. Among the eleven cases treated by both methods in separate episodes of G.A. the therapeutic response to triamcinolone and saline appeared the same in four, but the rest cleared more readily with triamcinolone. The diffuse G.A. cases appeared to respond in a similar way to the nodular forms. Three of the five cases of N.B.L. showed gradual resolution after a small number of treatments.
88
G.Sparrow and E.Abell
Subsequent observation over 1-12 months (mean 8) failed to show signs of recurrence. Slight hyperpigmentation persisted in the areas of treatment, but progressively faded. A patient with classical N.B.L. of the shins had repeated injections over a 2-year period, with gradual but partial improvement. The patient unchanged by treatment had atypical necrobiosis of the face alone. This spontaneously cleared during a pregnancy, only to relapse during the puerperium. Complications
Transient atrophy at the injection sites of triamcinolone was an almost constant finding in resolving G.A. lesions. However, even saline treated lesions often showed some erythema on clearing. In one case of N.B.L. multiple tiny ulcers appeared at the injection sites. These healed spontaneously less than 3 months later and subsequent injections were given cautiously and without further complications. In certain situations great difficulty occurred in penetrating into G.A. lesions. Nodules of the fingers, especially those set around the interphalangeal joints, were often inadequately infiltrated. Repeated attempts at injecting these sites were sometimes successful, but a proportion of failures was due to this problem. Some slight discomfort is produced by this injector but it was never sufficient to prevent continued treatment. DISCUSSION
The lack of substantial information on the efficacy of treatment in G.A. makes it impossible usefully to compare these results with previous reports. However, Kern & Schiff reported success in 3 of 4 cases treated with a number of compounds, while Wells & Smith commented that the rate of resolution did not seem to be aifected by various treatment methods, or by biopsy. These treatments included vitamin E (27 cases), elastoplast occlusion (19), CO, snow (13), X-ray (8) and intralesional hydrocortisone (4). Our results suggest that nearly 70% of patients with G.A. injeaed with triamcinolone can expect to gain complete resolution promptly. Saline injections were noticeably less effective but frequently produced an initially better cosmetic effect due to the lack of atrophy. Treatment with saline at first is probably well worthwhile before using triamcinolone. The high recurrence rate in each treatment group corresponds closely with the figure of 41",, for natural recurrence described by Wells & Smith (1963). Although these figures are high, the method does allow for rapid retreatment. The use of triamcinolone injections in N.B.L. certainly appears to be worthy of consideration, particularly if the condition can be treated before the onset of severe atrophy and ulceration. Whether injection of such advanced cases is justifiable seems doubtful. Our results seem to compare well with those obtained by Marten & Dulake, and, with care, ulceration from injection can be prevented. ACKNOWLEDGMENTS
We wish to record our thanks to the many physicians at St John's Hospital who referred their patients for treatment. We are also indebted to Mr Waller for supply of sterile fluids for injection and to the Department of Medical Illustration for the illustrations. REFERENCES KEBN, A.B. & SCHIFF, B.L. (i960) Injection therapy of granuloma annulare. Archives of Dermatology, Si, 969.
Granuloma annulare and necrobiosis lipoidica treated by jet injector
89
MARTEN, R . H . & DULAKE, M . (1957) Hydrocortisone in necrobiosis lipoidica diabeticorum. British Journal of Dermatology, 69, 395. NEWMAN, B.A. & FELDMAN, F . F . (1951) Effects of topical cortisone on chronic discoid lupus erythematosus and necrobiosis lipoidica diabeticorum. Journal of Investigative Dermatology, 17, 3. NYLEN, B.O. & SKOOG, T . (1958) Surgical treatment of necrobiosis lipoidica. Acta dermato-venereologica, 38, 366. ROLLINS, T . G . & WINKELMANN, R.K. (196c) Necrobiosis lipoidica granulomatosis. Archives of Dermatology, 82, 537. SAVITT, L.E. (1955) Favourable response of necrobiosis lipoidica diabeticorum to hydrocortisone suspension. Archives of Dermatology, 71, 506. VERBOV, J . L . & ABELLJ E . (1970) Jet gun intralcsional therapy. Transactions of the St John's Hospital Dertnatological Society, 56, 39. WELLS, R . S . & SMITH, M.A. (1963) The natural history of granuloma annulare. British Journal of Dermatology, 75, 199WILSON JONES, E. (1971) Necrobiosis lipoidica presenting on the face and scalp. Transactions of the St John's Hospital Dermatological Society, 57, 202.
Granuloma annulare and necrobiosis lipoidica treated by jet injector G.SPARROW AND E.ABELL St John's Hospital for Diseases of the Skin, London W.C.2 Accepted for publication 25 October 1974
SUMMARY
A Porto-jet injector was employed to treat forty-five cases of granuloma annulare and five cases of necrobiosis lipoidica with triamcinolone acetonide or sterile normal saline. Complete clearance of granuloma annulare lesions was achieved in nearly 70",, of those receiving triamcinolone and in 44% with saline. Inadequate penetration of lesions was responsible for a number of failures. The rate of recurrence after treatment was high but retreatment was usually successful. In three cases of necrobiosis lipoidica complete resolution occurred, while in one, partial improvement was obtained. No serious complications of this type of treatment were observed.
Granuloma annulare (G.A.) is a benign condition which frequently presents a therapeutic problem. It runs a variable course before ultimate spontaneous resolution but this course is often very protracted. In a series of 115 cases (Wells & Smith, 1963), only half resolved within 2 years, while the overall duration varied from 3 months to 25 years. In addition, even after spontaneous clearance, 41" „ of their patients had one or more recurrences, which although usually resolving more quickly than the primary lesion were, none the less, persistent. Many methods of treatment have been advocated but little information appears to exist about their effectiveness. Intra-lesional injection has been employed, and in a small series reported by Kern & Schiff (i960) it was suggested that hydrocortisone, saline, sterile water, procaine and xylocaine could be used equally successfully. Necrobiosis lipoidica (N.B.L.), whether associated with diabetes or not, also undergoes spontaneous healing, but very infrequently (Rollins & Winkelmann, i960). Topical corticosteroids (Savitt, 1955; Newman & Feldman, 1951) and surgical excision and grafting (Nylen & Skoog, 1958) have been advocated as treatment. Injections of hydrocortisone have also been used with success in four patients reported by Marten & Dulake (1957), using conventional methods. This study details the results obtained after the treatment of a large series of patients with G.A., using a Porto-jet needleless injector. An attempt has been made to assess both the effect of saline and triamcinolone acetonide and also the frequency of recurrence following clearance induced by treatment. Five cases of N.B.L. are also included. 85
G.Sparrow and E.Abell
86
MATERIALS AND METHODS
Forty-five patients with G.A. and five with N.B.L. were treated. They ranged in age from 8 to 73 years and consisted of 35 females and 15 males. In twenty-seven, the diagnosis was confirmed by biopsy. One patient with G.A. and two with N.B.L. were diabetic, while eight patients with G.A. gave a family history of diabetes. The mean duration of the G.A. was 3 years (range 5 months to 15 years); only six patients were recorded to have had previous spontaneous clearance. Two of the cases of N.B.L. had atypical annular necrobiosis of the face (Wilson Jones, 1971), confirmed by biopsy. One of these had a combination of annular lesions on die back and face, with typical necrobiosis lipoidica on the shins. The other had G.A.-like lesions on the elbows. In none of the cases of N.B.L. had the condition progressed to severe atrophy or ulceration. Injections of 01 ml triamcinolone acetonide (5 mg/ml) or of sterile normal saline were delivered into the G.A. lesions to produce even infiltration. The plaques of N.B.L. were infiltrated around the active margins before the central areas were treated. Great care was taken to avoid injecting areas of marked atrophy. Injections were performed with a Porto-jet needleless injector as described previously (Verbov & Abell, 1970). Initially patients were treated with a series of three injections at 2weekly intervals, but this was subsequently modified as single injections gave similar results on followup. Subsequently injection given at 6- to 8-weekly intervals were performed as indicated by the clinical situation. The number of treatments varied from i to 16 (mean 2-4) and the follow up period from 2 months to 2 years (mean 4-5 months). For assessment purposes, results were grouped as follows: (a) Complete clearance of all treated lesions. (b) Partial clearance. (c) No change. Five cases in which initial partial improvement was followed by rapid relapse were assessed as being unchanged. Twenty-six and twenty-five patients with the nodular form of G.A. received sterile normal saline and triamcinolone acetonide respectively. Eleven patients in each group received both types of therapy for separate lesions. Five patients with diffuse G.A. and the five with N.B.L. were treated with triamcinolone acetonide. TABLE I. Injection treatment of granuloma annulare Results Cases
Mean no. treatments
Mean no. injections
Complete clearance
Partial clearance
No change
Recurred
Triamcinolone acetorade
Nodular Diffuse
25
29
32 S4
17(68%) 6(24%) 3 1 1
2(8%) -
8(47%)
1-6 I
34 18
12 (44%) 9 (33%)
6 (22%)
5
5
Normal saline
Nodular Diffuse
27 I
RESULTS
Complete clearance of G.A. lesions was achieved in 17 of 25 (68",,) treated with triamcinolone (Figs. I and 2) and in 12 of 27 (44%) using sterile saline; in both groups the recurrence rate was high, being
Granidoma annulare and necrobiosis lipotdica treated by jet injector
FIGURE I. Granuloma annulare before treatmeni.
FIGURE 2. Granuloma annulare 5 months after treatment (triamcinolone acetonide).
8 and 5 respectively. Resolution usually took 2-4 weeks after successful injection and recurrences appeared within 3-7 months of the time of initial treatment. Thirteen of these patients with recurrent lesions were retreated, only one of whom failed to respond. Certain patterns of response appeared during the follow-up. Over half the patients responded by rapid and complete clearance with a small number of injections (1-3). In a small group improvement occurred in the sites injected coincidental with the development of new lesions elsewhere. This led to prolonged periods of treatment. Among the eleven cases treated by both methods in separate episodes of G.A. the therapeutic response to triamcinolone and saline appeared the same in four, but the rest cleared more readily with triamcinolone. The diffuse G.A. cases appeared to respond in a similar way to the nodular forms. Three of the five cases of N.B.L. showed gradual resolution after a small number of treatments.
88
G.Sparrow and E.Abell
Subsequent observation over 1-12 months (mean 8) failed to show signs of recurrence. Slight hyperpigmentation persisted in the areas of treatment, but progressively faded. A patient with classical N.B.L. of the shins had repeated injections over a 2-year period, with gradual but partial improvement. The patient unchanged by treatment had atypical necrobiosis of the face alone. This spontaneously cleared during a pregnancy, only to relapse during the puerperium. Complications
Transient atrophy at the injection sites of triamcinolone was an almost constant finding in resolving G.A. lesions. However, even saline treated lesions often showed some erythema on clearing. In one case of N.B.L. multiple tiny ulcers appeared at the injection sites. These healed spontaneously less than 3 months later and subsequent injections were given cautiously and without further complications. In certain situations great difficulty occurred in penetrating into G.A. lesions. Nodules of the fingers, especially those set around the interphalangeal joints, were often inadequately infiltrated. Repeated attempts at injecting these sites were sometimes successful, but a proportion of failures was due to this problem. Some slight discomfort is produced by this injector but it was never sufficient to prevent continued treatment. DISCUSSION
The lack of substantial information on the efficacy of treatment in G.A. makes it impossible usefully to compare these results with previous reports. However, Kern & Schiff reported success in 3 of 4 cases treated with a number of compounds, while Wells & Smith commented that the rate of resolution did not seem to be aifected by various treatment methods, or by biopsy. These treatments included vitamin E (27 cases), elastoplast occlusion (19), CO, snow (13), X-ray (8) and intralesional hydrocortisone (4). Our results suggest that nearly 70% of patients with G.A. injeaed with triamcinolone can expect to gain complete resolution promptly. Saline injections were noticeably less effective but frequently produced an initially better cosmetic effect due to the lack of atrophy. Treatment with saline at first is probably well worthwhile before using triamcinolone. The high recurrence rate in each treatment group corresponds closely with the figure of 41",, for natural recurrence described by Wells & Smith (1963). Although these figures are high, the method does allow for rapid retreatment. The use of triamcinolone injections in N.B.L. certainly appears to be worthy of consideration, particularly if the condition can be treated before the onset of severe atrophy and ulceration. Whether injection of such advanced cases is justifiable seems doubtful. Our results seem to compare well with those obtained by Marten & Dulake, and, with care, ulceration from injection can be prevented. ACKNOWLEDGMENTS
We wish to record our thanks to the many physicians at St John's Hospital who referred their patients for treatment. We are also indebted to Mr Waller for supply of sterile fluids for injection and to the Department of Medical Illustration for the illustrations. REFERENCES KEBN, A.B. & SCHIFF, B.L. (i960) Injection therapy of granuloma annulare. Archives of Dermatology, Si, 969.
Granuloma annulare and necrobiosis lipoidica treated by jet injector
89
MARTEN, R . H . & DULAKE, M . (1957) Hydrocortisone in necrobiosis lipoidica diabeticorum. British Journal of Dermatology, 69, 395. NEWMAN, B.A. & FELDMAN, F . F . (1951) Effects of topical cortisone on chronic discoid lupus erythematosus and necrobiosis lipoidica diabeticorum. Journal of Investigative Dermatology, 17, 3. NYLEN, B.O. & SKOOG, T . (1958) Surgical treatment of necrobiosis lipoidica. Acta dermato-venereologica, 38, 366. ROLLINS, T . G . & WINKELMANN, R.K. (196c) Necrobiosis lipoidica granulomatosis. Archives of Dermatology, 82, 537. SAVITT, L.E. (1955) Favourable response of necrobiosis lipoidica diabeticorum to hydrocortisone suspension. Archives of Dermatology, 71, 506. VERBOV, J . L . & ABELLJ E . (1970) Jet gun intralcsional therapy. Transactions of the St John's Hospital Dertnatological Society, 56, 39. WELLS, R . S . & SMITH, M.A. (1963) The natural history of granuloma annulare. British Journal of Dermatology, 75, 199WILSON JONES, E. (1971) Necrobiosis lipoidica presenting on the face and scalp. Transactions of the St John's Hospital Dermatological Society, 57, 202.
