JEADV
DOI: 10.1111/jdv.12283
SHORT REPORT
Proximal nail fold intralesional steroid injection responsible syndrome for Hoigne R. Baran* Dermatology, Nail Disease Centre, Cannes, France *Correspondence: R. Baran. E-mails: [email protected]; [email protected]
Abstract syndrome is the most common name given to a condition which has been called in different Background Hoigne ways. Objective We want to show that an intralesional injection of prednisolone into the proximal nail fold may produce dorsal pain, dyspnoea and headaches within the 2 min following the injection and to explain the pathophysiology of his condition. syndrome by comparing the size of the crystals taking Methods We studied the different drugs responsible for Hoigne into account the diameter of pulmonary capillaries. The drug Company informed us that the size of the microcrystals were 2–4 lm vs. the 8 lm on average of the diameter of the pulmonary capillaries. syndrome can be explained, especially the neuropsychiatric and neuropulmoConclusion All the symptoms of Hoigne nary ones. Therefore, dermatologists should be aware of this phenomenon when they inject steroids in psoriatic nail patients. Received: 4 September 2013; Accepted: 16 September 2013
Conflicts of interest None declared.
Funding sources None declared.
A 38-year-old male patient was referred to us because he was complaining of alterations of the dorsum of both thumb nail plates. This condition was due to a nervous habit of repeatedly pushing back the cuticle on one or several fingers which can create ‘washboard nails’, also known as the habit-tic deformity (Fig 1). Usually, as in this subject, the proximal nail fold (PNF) of the thumbs is damaged by the index finger and may show prominent swelling, redness and thin scaling. This chronic, mechanical injury results in a series of transverse grooves and a large central depression running down the nail. We explained to the patient that this habit-tic deformity could respond to systemic treatment with antidepressant serotonin reuptake inhibitors, which are used for obsessive–compulsive disorders. However, our patient preferred the alternative we suggested, i.e. protection of the distal phalanx of both thumbs with a daily application of an occlusive dressing for 6 months (sheer microporeâ, St. Paul, MN, USA) which often solves the problem. To rapidly diminish the pressure exerted on the nail matrix by the oedema of the PNF (Fig 2), a 2/10 cc intralesional injection of prednisolone acetate was performed into the swollen PNF of
JEADV 2014, 28, 1563–1565
both thumbs. Within the 2–3 min following the second injection into the PNF, the patient experienced pain laterally to the lumbar spine, followed 1 min later by difficult breathing combined with anxiety, panic disorder and dire fear, especially when strong headaches also appeared. Pulse and blood pressure were normal. The patient lay down and accepted to drink a glass of cold water. All these signs progressively disappeared after about 15 min and the patient, still slightly anxious, gave a long sigh of relief. The patient had experienced Hoigne syndrome. The frequent signs and symptoms mentioned in various sources concerning this syndrome include psychiatric, neurological, respiratory and cardiovascular troubles. Most case reports involve reactions to intravenous or more often intramuscular administrated penicillin. The symptoms include psychomotor agitation, panic-like anxiety, fear of death, alteration of consciousness, seizures, confusion and even hallucinations. The neuropsychiatric symptoms tend to be accompanied by tachycardia, hypertension, dyspnoea and numbness of the extremities. However, Hoigne syndrome rarely involves all of these symptoms and our patient only experienced mild symptoms.
© 2013 European Academy of Dermatology and Venereology
Baran
1564
Anaphylactic reaction starts 30 min after the injection and may be associated with hypotension and angioedema, which has never been observed in Hoigne syndrome. Jarisch–Herxheimer reaction in syphilis appears 12 h after the first intramuscular injection and a vagal reaction, due to the fear of pain, can occur even before the injection, when the patient simply sees the needle.
Pathophysiology
Figure 1 Washboard nail with oedema of the proximal nail fold (PNF).
Figure 2 Technique used for injecting steroids into the proximal nail fold (PNF) in psoriatic nail (Courtesy of S. Goettmann, France).
First described by Batchelor1 in 1959 the condition was later called Hoigne syndrome.2 Different names have since been given to this syndrome:3 immediate non-allergic psychotic reaction,4 delusions induced by procaine penicillin,5 reactions to aqueous procaine penicillin,6 pseudo-anaphylactic reactions from inadvertent infusion of procaine penicillin7 as well as antibiomania.8,9 The clinical manifestations start within a few seconds following the injection, which is the major diagnostic criteria, and we wonder if antibiomania, a rare, serious, idiosyncratic side effect following oral clarithromycin really belongs to Hoigne syndrome. The differential diagnosis includes anaphylactic, Herxheimer and vasovagal reaction.2
JEADV 2014, 28, 1563–1565
For Kryst and Wanyura10 the complex of short-lasting symptoms characterized by severe agitation with confusion, visual and auditory hallucinations and dire fear is caused by accidental penetration of a certain amount of intramuscular penicillin injected into the venous system with a poor technique or to a great number of injections in a limited area. This contrasts with Hoigne’s opinion.2 A perfect technique of intramuscular injection does not preclude penetration of the drug into the vascular system. If we admit that the microcrystals of procaine penicillin reach the brain through the blood stream, it may be considered that the clinical signs of Hoigne syndrome are a manifestation of cerebral embolism resulting in kindling11 or focal ischemia particularly involving temporal and limbic structures. This hypothesis is, however, contradicted by Schmied et al.,2 because the diameter of pulmonary capillaries is on average 8 lm. Such a filter can retain most of the microcrystals of procaine penicillin, the size of which is between 5 and 100 lm. Trapped in the pulmonary capillaries stream, the drug should not be able to reach the brain. Bredt12 suggests that a small number of tiny crystals may dissolve when they penetrate a blood vessel. Bigger crystals will flow with the blood stream until they are trapped by pulmonary capillaries at which point the patient may develop symptoms of dyspnoea. Concerning our case, the company Sanofi-Aventis informed us that the size of the microcrystals was 2–4 lm. Another case; similar to ours, of tiny crystals reaching the brain was reported by Humbert et al.3 Half a cc of triamcinolone 40 mixed with half a cc of lidocaine was injected into a keloid of the abdomen of a 13-year-old girl who then experienced Hoigne syndrome. The size of 20% of the crystals was between 1 and 10 lm. Therefore, the characteristics of acute symptoms and clinical course of Hoigne syndrome depend upon the size of the particles of the drug, which accidentally penetrate a blood vessel due to their solubility in the blood, and the occasional chance of them getting through pulmonary capillaries. Consequently, the neuropsychiatric symptoms are interpreted as an indication that the temporo-limbic structures of the brain may be involved in this reaction. Nevertheless, the suggestion that the limbic system sensitization (i.e. kindling), which might explain the susceptibility to the neuropsychiatric symptoms of Hoigne syndrome in individuals repeatedly exposed to a drug, may be rejected in
© 2013 European Academy of Dermatology and Venereology
syndrome Hoigne
most cases, especially when it appears after the first intramuscular injection of a new drug. In conclusion, the different names given to this syndrome summarize our knowledge. In our opinion, the aetiology of the case presented here is definitely in favour of the size of the crystals as being the main culprit when injected into the venous blood stream. It explains the dyspnoea, headaches and the dire fear of the patient as small crystals reach the temporo-limbic area.13 It shows that only very small crystals are responsible. This is a warning to dermatologists, who inject steroids into the PNF in psoriatic individuals and is also the first case ever in the literature.
References 1 Batchelor RC, Horne GD, Rogerson HL. An unusual reaction to procaine penicillin in aqueous suspension. Lancet 1951; 2: 195–198. 2 Schmied C, Schmied E, Vogel J, Saurat JH. Syndrome de Hoigne ou reaction pseudo-anaphylactique a la procaine-penicilline G: un classique d’actualite. Schweiz Med Wochenschr 1990; 120: 1045–1049. 3 Humbert Ph, Girardin P, Aubin F. Sensation de mort imminente lors d’une infiltration par acetonide de triamcinolone et lidoca€ıne: l’effet Hoigne. Ann Dermatol Venereol 2001; 128: 762.
JEADV 2014, 28, 1563–1565
1565
4 Einterz EM, Einterz RM. Immediate nonallergic psychotic reaction to intramuscular procaine penicillin. Int J Dermatol 1995; 34: 627–629. 5 Cummings JL, Barritt CF, Horan M. Delusions induced by procaine penicillin: case report and review of the syndrome. Int J Psychiatry Med 198687; 16:163–168. 6 Utley PM, Lucas JB, Billings TE. Acute psychotic reactions to aqueous procaine penicillin. South Med J 1966; 59: 1271–1274. 7 Galpin JE, Chow AW, Joshikawa TT et al. Pseudo-anaphylactic reactions from inadvertent infusion of procaine-penicillin G. Ann Intern Med 1974; 81: 358–359. 8 Przybylo HJ, Przybylo JH, Todd D, Cote CJ. Acute psychosis after anesthesia: the case for antibiomania. Paediatr Anaesth 2005; 15: 703–705. 9 Rallis E, Moussatou V, Saltos L. Clarithromycin-induced Hoigne syndrome in a patient treated for rosacea. J Eur Acad Dermatol Venereol 2009; 23: 1093–1094. 10 Kryst L, Wanyura H. Hoigne’s syndrome – its course and symptomatology. J Maxillofac Surg 1979; 7: 320–326. 11 Bell RC, Rannie I, Wynne NA. Adverse reactions to procaine-penicillin in cats and man. Lancet 1954; II: 62–66. 12 Bredt J. Akute nicht-allergische Reaktionen bei Anwendung von DepotPenicillin. Dtsch Med Wochenschr 1965; 90: 1559. 13 Araskiewicz A, Rybakowski JK. Hoigne’s syndrome: a procaine-induced limbic kindling. Med Hypotheses 1994; 42: 261–264.
© 2013 European Academy of Dermatology and Venereology
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
DOI: 10.1111/jdv.12283
SHORT REPORT
Proximal nail fold intralesional steroid injection responsible syndrome for Hoigne R. Baran* Dermatology, Nail Disease Centre, Cannes, France *Correspondence: R. Baran. E-mails: [email protected]; [email protected]
Abstract syndrome is the most common name given to a condition which has been called in different Background Hoigne ways. Objective We want to show that an intralesional injection of prednisolone into the proximal nail fold may produce dorsal pain, dyspnoea and headaches within the 2 min following the injection and to explain the pathophysiology of his condition. syndrome by comparing the size of the crystals taking Methods We studied the different drugs responsible for Hoigne into account the diameter of pulmonary capillaries. The drug Company informed us that the size of the microcrystals were 2–4 lm vs. the 8 lm on average of the diameter of the pulmonary capillaries. syndrome can be explained, especially the neuropsychiatric and neuropulmoConclusion All the symptoms of Hoigne nary ones. Therefore, dermatologists should be aware of this phenomenon when they inject steroids in psoriatic nail patients. Received: 4 September 2013; Accepted: 16 September 2013
Conflicts of interest None declared.
Funding sources None declared.
A 38-year-old male patient was referred to us because he was complaining of alterations of the dorsum of both thumb nail plates. This condition was due to a nervous habit of repeatedly pushing back the cuticle on one or several fingers which can create ‘washboard nails’, also known as the habit-tic deformity (Fig 1). Usually, as in this subject, the proximal nail fold (PNF) of the thumbs is damaged by the index finger and may show prominent swelling, redness and thin scaling. This chronic, mechanical injury results in a series of transverse grooves and a large central depression running down the nail. We explained to the patient that this habit-tic deformity could respond to systemic treatment with antidepressant serotonin reuptake inhibitors, which are used for obsessive–compulsive disorders. However, our patient preferred the alternative we suggested, i.e. protection of the distal phalanx of both thumbs with a daily application of an occlusive dressing for 6 months (sheer microporeâ, St. Paul, MN, USA) which often solves the problem. To rapidly diminish the pressure exerted on the nail matrix by the oedema of the PNF (Fig 2), a 2/10 cc intralesional injection of prednisolone acetate was performed into the swollen PNF of
JEADV 2014, 28, 1563–1565
both thumbs. Within the 2–3 min following the second injection into the PNF, the patient experienced pain laterally to the lumbar spine, followed 1 min later by difficult breathing combined with anxiety, panic disorder and dire fear, especially when strong headaches also appeared. Pulse and blood pressure were normal. The patient lay down and accepted to drink a glass of cold water. All these signs progressively disappeared after about 15 min and the patient, still slightly anxious, gave a long sigh of relief. The patient had experienced Hoigne syndrome. The frequent signs and symptoms mentioned in various sources concerning this syndrome include psychiatric, neurological, respiratory and cardiovascular troubles. Most case reports involve reactions to intravenous or more often intramuscular administrated penicillin. The symptoms include psychomotor agitation, panic-like anxiety, fear of death, alteration of consciousness, seizures, confusion and even hallucinations. The neuropsychiatric symptoms tend to be accompanied by tachycardia, hypertension, dyspnoea and numbness of the extremities. However, Hoigne syndrome rarely involves all of these symptoms and our patient only experienced mild symptoms.
© 2013 European Academy of Dermatology and Venereology
Baran
1564
Anaphylactic reaction starts 30 min after the injection and may be associated with hypotension and angioedema, which has never been observed in Hoigne syndrome. Jarisch–Herxheimer reaction in syphilis appears 12 h after the first intramuscular injection and a vagal reaction, due to the fear of pain, can occur even before the injection, when the patient simply sees the needle.
Pathophysiology
Figure 1 Washboard nail with oedema of the proximal nail fold (PNF).
Figure 2 Technique used for injecting steroids into the proximal nail fold (PNF) in psoriatic nail (Courtesy of S. Goettmann, France).
First described by Batchelor1 in 1959 the condition was later called Hoigne syndrome.2 Different names have since been given to this syndrome:3 immediate non-allergic psychotic reaction,4 delusions induced by procaine penicillin,5 reactions to aqueous procaine penicillin,6 pseudo-anaphylactic reactions from inadvertent infusion of procaine penicillin7 as well as antibiomania.8,9 The clinical manifestations start within a few seconds following the injection, which is the major diagnostic criteria, and we wonder if antibiomania, a rare, serious, idiosyncratic side effect following oral clarithromycin really belongs to Hoigne syndrome. The differential diagnosis includes anaphylactic, Herxheimer and vasovagal reaction.2
JEADV 2014, 28, 1563–1565
For Kryst and Wanyura10 the complex of short-lasting symptoms characterized by severe agitation with confusion, visual and auditory hallucinations and dire fear is caused by accidental penetration of a certain amount of intramuscular penicillin injected into the venous system with a poor technique or to a great number of injections in a limited area. This contrasts with Hoigne’s opinion.2 A perfect technique of intramuscular injection does not preclude penetration of the drug into the vascular system. If we admit that the microcrystals of procaine penicillin reach the brain through the blood stream, it may be considered that the clinical signs of Hoigne syndrome are a manifestation of cerebral embolism resulting in kindling11 or focal ischemia particularly involving temporal and limbic structures. This hypothesis is, however, contradicted by Schmied et al.,2 because the diameter of pulmonary capillaries is on average 8 lm. Such a filter can retain most of the microcrystals of procaine penicillin, the size of which is between 5 and 100 lm. Trapped in the pulmonary capillaries stream, the drug should not be able to reach the brain. Bredt12 suggests that a small number of tiny crystals may dissolve when they penetrate a blood vessel. Bigger crystals will flow with the blood stream until they are trapped by pulmonary capillaries at which point the patient may develop symptoms of dyspnoea. Concerning our case, the company Sanofi-Aventis informed us that the size of the microcrystals was 2–4 lm. Another case; similar to ours, of tiny crystals reaching the brain was reported by Humbert et al.3 Half a cc of triamcinolone 40 mixed with half a cc of lidocaine was injected into a keloid of the abdomen of a 13-year-old girl who then experienced Hoigne syndrome. The size of 20% of the crystals was between 1 and 10 lm. Therefore, the characteristics of acute symptoms and clinical course of Hoigne syndrome depend upon the size of the particles of the drug, which accidentally penetrate a blood vessel due to their solubility in the blood, and the occasional chance of them getting through pulmonary capillaries. Consequently, the neuropsychiatric symptoms are interpreted as an indication that the temporo-limbic structures of the brain may be involved in this reaction. Nevertheless, the suggestion that the limbic system sensitization (i.e. kindling), which might explain the susceptibility to the neuropsychiatric symptoms of Hoigne syndrome in individuals repeatedly exposed to a drug, may be rejected in
© 2013 European Academy of Dermatology and Venereology
syndrome Hoigne
most cases, especially when it appears after the first intramuscular injection of a new drug. In conclusion, the different names given to this syndrome summarize our knowledge. In our opinion, the aetiology of the case presented here is definitely in favour of the size of the crystals as being the main culprit when injected into the venous blood stream. It explains the dyspnoea, headaches and the dire fear of the patient as small crystals reach the temporo-limbic area.13 It shows that only very small crystals are responsible. This is a warning to dermatologists, who inject steroids into the PNF in psoriatic individuals and is also the first case ever in the literature.
References 1 Batchelor RC, Horne GD, Rogerson HL. An unusual reaction to procaine penicillin in aqueous suspension. Lancet 1951; 2: 195–198. 2 Schmied C, Schmied E, Vogel J, Saurat JH. Syndrome de Hoigne ou reaction pseudo-anaphylactique a la procaine-penicilline G: un classique d’actualite. Schweiz Med Wochenschr 1990; 120: 1045–1049. 3 Humbert Ph, Girardin P, Aubin F. Sensation de mort imminente lors d’une infiltration par acetonide de triamcinolone et lidoca€ıne: l’effet Hoigne. Ann Dermatol Venereol 2001; 128: 762.
JEADV 2014, 28, 1563–1565
1565
4 Einterz EM, Einterz RM. Immediate nonallergic psychotic reaction to intramuscular procaine penicillin. Int J Dermatol 1995; 34: 627–629. 5 Cummings JL, Barritt CF, Horan M. Delusions induced by procaine penicillin: case report and review of the syndrome. Int J Psychiatry Med 198687; 16:163–168. 6 Utley PM, Lucas JB, Billings TE. Acute psychotic reactions to aqueous procaine penicillin. South Med J 1966; 59: 1271–1274. 7 Galpin JE, Chow AW, Joshikawa TT et al. Pseudo-anaphylactic reactions from inadvertent infusion of procaine-penicillin G. Ann Intern Med 1974; 81: 358–359. 8 Przybylo HJ, Przybylo JH, Todd D, Cote CJ. Acute psychosis after anesthesia: the case for antibiomania. Paediatr Anaesth 2005; 15: 703–705. 9 Rallis E, Moussatou V, Saltos L. Clarithromycin-induced Hoigne syndrome in a patient treated for rosacea. J Eur Acad Dermatol Venereol 2009; 23: 1093–1094. 10 Kryst L, Wanyura H. Hoigne’s syndrome – its course and symptomatology. J Maxillofac Surg 1979; 7: 320–326. 11 Bell RC, Rannie I, Wynne NA. Adverse reactions to procaine-penicillin in cats and man. Lancet 1954; II: 62–66. 12 Bredt J. Akute nicht-allergische Reaktionen bei Anwendung von DepotPenicillin. Dtsch Med Wochenschr 1965; 90: 1559. 13 Araskiewicz A, Rybakowski JK. Hoigne’s syndrome: a procaine-induced limbic kindling. Med Hypotheses 1994; 42: 261–264.
© 2013 European Academy of Dermatology and Venereology
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
