Reach Us +32-28-08-6657

Gardner-Diamond’s Syndrome: Literature review

Juliana Vega Miranda1 and Basilio Vagner2,3*
  1. Physician Pontifical Bolivarian University Resident of Internal Medicine, Pontifical Bolivarian University, Pablo Tobón Uribe Hospital, Medellín, Colombia
  2. Clinical Neurology Specialist, Neurology Division Director, Pablo Tobón Uribe Hospital, Medellín, Colombia
  3. Clinical Neurology, School of Medicine, Pontifical Bolivarian University and CES University, Medellin, Colombia
Corresponding Author: Basilio Vagner; Neurology Division Director, Pablo Tobón Uribe Hospital, Medellín, Colombia, Tel: (574) 4459000, Fax: (574) 4459758, Email: [email protected]
Related article at Pubmed, Scholar Google


Gardner Diamond’s Syndrome is a rare autoimmune vasculopathy of little known etiology. It consists of outbreaks of painful atraumatic ecchymotic lesions in any part of the body, particularly in the lower limbs and thorax of young women, associated to the appearance of psychiatric imbalance or disorders, suggesting emotional distress as the main trigger and perpetuator of such lesions.


Gardner Diamond, Autoimmune Vasculopathy, Emotional Stress


Gardner Diamond Syndrome (Autoerythrocyte sensitization syndrome, Psychogenic purpura)1 is a rare autoimmune vasculopathy2 of little known etiology. In a psychiatric or subjacent psychosomatic disorder context, it is a clinical profile characterized by atraumatic painful ecchymotic lesions.3-4
It follows a path of relatively benign, variable severity, with relapse-remission behavior, and recurrence of lesions even after 38 years from the start of the disease5- 6
Descriptions from the early XX century are found in literature:
Schindler, 1927, described 16 patients with similar skin hemorrhages, stating such lesions disappeared after several sessions of hypnosis.
Jacobi, 1929, described two cases of patients with purpura and psychiatric associated disorders. Nevertheless, the first official reports are from 1955 when Gardner and Diamond described the entity in four women5. Later, Ratnoff and Agle named it Psychogenic purpura due to the association with psychiatric disorders7 Current literature on this matter is based on cases reported (162 up to 2009, of which only ten involve men) 2-8-9-10 In 1971 Lababidi & Friedman, described the first case of Psychogenic purpura in a man; after that, cases describe on the male sex are but a few, most of them take place during the third decade of life with lesions similar to those found on women. It is assumed that men make up 5% of the frequency of the disease 11-12-13 Ratnoff reported the largest series of cases in 1989. This author describes 71 patients, most of them females, with lesions compatible with such entity; the ecchymoses appear weeks or days after trauma or surgery, but the most frequently related factor was emotional stress. The response to the skin test (see below) was erratic, only 59% of all patients had a positive response. Among the non-skin manifestations, patients presented cephalea, paraesthesia, syncope and diplopia (in some cases monocular). The prevailing psychiatric disorders were depression, sexual difficulties, and obsessive-compulsive disorders. 14


As mentioned before, it is a rare entity from which we have little accurate statistic data. Hitherto an entity prevailing in women, approaching their thirties (and varying between 19-72 years of age), however cases on men and children have also been reported6


Little has been stated about the etiology of the entity. Multiple factors related to appearances of lesions have been suggested, including immunologic, hematologic, hormonal, vascular and subjacent inflammatory conditions 15-16; also, associations between the neuroendocrine axis and behavior have been studied seeking to explain the way in which psychiatric disorders have somatic manifestations. 17
Immunological/inflammatory: In principle we are dealing with an autoimmune vasculopathy, of which phosphatidylserine, an erythrocyte membrane phospholipide1, appears as its primary antigen. Also suggested were blood cell or vascular endothelial stroma - or structure – distortion, and oxidative distress-induced damage, causing a phenomenon of local inflammation in predisposed subjects. Strunecka, using indirect immune fluorescence (IIF), showed that over 50% of the phosphatidylserine present on GDS patients´ RBCs is redistributed over the outer cell membrane layer5,18-19-20-21 Similar inflammatory phenomena have been recounted after exposure to other substances such as Serum, platelets, proteic derivates, histamine, histidine, serotonin, tryptophan, trypsin, DNA and copper6-22-23 It has been related to immunologic phenomena, taking into account reported cases in patients with autoimmune diseases like SLE, immune complex nephritis, idiopathic thrombocytopenic purpura; as well as those with low complement levels24 and positive anticardiolipin antibodies1; establishing scenarios in which there may be deterioration of symptoms following emotional distress and where use of oral steroids might be useful for treatment.
Vascular: Merlen suggested regulation alteration in venous capillary tonus by fluctuations in the kinin-kallikrein system; related to fibrin endothelial synthesis alteration.5-25
Hematological: this work has been postulated to account for reports of platelet dysfunction, thrombocytosis, entity related platelet III factor deficiency 6-26; although hemostasia assessing paraclinicals appear normal in these patients, there seems to exist a defect in the primary hemostasia, considering that 2/3 of the patients present menorrhagia, epistaxis, gingivorrhagia and gastro-intestinal bleeding 3-4 some authors suggest an increase in plasmatic fibrinolytic activity along with secondary bleeding27
The etiological component of emotional stress on the genesis of lesions is not clear, however the neuroimmune system is deemed as mediator on the appearance of lesions. 28-29


The disease development it’s usually preceded by a series of mechanical wounds (surgery or trauma) 30 by which blood extravasation and exposure to antigens. It is clear though, that emotional stress acts as main trigger and perpetuator of the lesions 3. Also, cases were symptoms are worsened by exposure to copper have been reported: a 19 year old patient presented symptoms improvement when her IUD (Intrauterine Dispositive) was removed and reappearance of the lesions with IUD reimplantation 31Skin symptoms are preceded by prodromes, general discomfort and fatigue. 2 Afterwards, lesions may appear in any part of the body (mainly on lower limbs and thorax and may even involve some areas of the face) 1
There is pain and pruritus in the skin area where lesions will appear; a skin induration may be observed after 4-5 hours, and in 24-48 hours it turns into a painful ecchymotic patch, 3-10 cm in diameter and lasting 1 or 2 days. After this time, the lesion starts discoloring until it turns yellowish before finally disappearing leaving no scars whatsoever in a matter of in 1 to 2 weeks. 2-5-32 As described in Table 1, over 50% of all patients present nonskin related symptoms 5-30-33-9-17-34. Manifestations are usually benign and carry a good prognosis; however the Gardner-Diamond Syndrome has been identified as the source of membranous glomerulopathy. 35
Associations with other pathologies as Glomerulonephritis, lymphoid interstitial pneumonia, angioimmunoblastic lymphadenopathy as well with two patients with Cerebrovascular disease (PVD)5 and compartment syndrome has been reported. Most frequent psychiatric disorders are depression, anxiety, emotional lability, guilt feelings, sexual issues, masochism, hysteric and borderline personality, and obsessive-compulsive behavior.


Histological studies on the ecchymotic lesions reveal skin edema, erythrocytes extravasation and perivascular acute inflammatory infiltration. some iron compatible pigmentation pools on macrophages, have also been observed. Atypical Leukocytoclastic changes may show on infiltration or fibrinoid degeneration of vessels. Diagnosis in most cases does not require hystopathological assessment.1-5


There are no GDS-lab specifics. Hematological parameters, including hemoglobin, hematocrit, platelets count, peripheral extension, globular sedimentation rate, electrolytes, bleeding time, prothrombin, thrombin, partial thromboplastin timing, and clotting factors, are usually within normal limits2, nevertheless there are reports of patients with typical lesions and thrombocytosis36


It is mainly clinic, where previous episodes of physical or emotional stress, combine with typical skin lesions, usually in women with regular coagulation parameters. With infiltration patches and plates, followed by inflammation and by areas of painful ecchymosis within the following 24 hours 37

Skin test:

Intradermic injection of 1ml of 80% washed erythrocytes suspension originated on the patient herself. This test is positive if GDS typical inflammatory lesions appear within 24 hours (there are reports of appearance of lesions 96 hours after injection)38, and then, gradually, a progression to ecchymosis takes place 2. The test is made in non-accessible hands skin areas to prevent factitious lesions. A negative test does not exclude diagnosis10.


Differential diagnostics include, among other coagulopathies 39, conditions related to bleeding such as idiopathic thrombocytopenic purpura; Henoch- Schoenlein purpura, Ehlers-Danlos Syndrome, contact Dermatitis, systemic erythematous lupus (SEL), Munchausen disease, compartment syndrome and Weber-Christian panniculitis2 Due to its low incidence in children, it is important to dismiss physical abusing as well as other pediatric psycho-cutaneous disorders (trichotillomania, psychogenic excoriation, acne, dermatophagia, etc.)10 It is important to tell it apart from other coagulation disorders such as acquired VIII factor inhibitor, hemophilic pseudo-tumor and skin necrosis related to cumarinics.40


The treatment of GDS is so difficult that this entity is also known as dermatosis sine therapia. There are neither sufficiently effective methods nor randomized studies to use as a reference point for choosing the best therapy. Steroids, antibiotics, analgesics, antihistaminics, glucocorticoids and cytostatics5-6-41 have been used, some patients presented remission with high doses of immunoglobulin42 with no clear benefit in any of them. Considering the underlying psychological context 1 all cases reported insist upon the relevance of psychotherapy. Hypnosis and psychotherapy were effective at improving skin lesions in young patients 10- 43-44-45 Using medications to regulate vascular tonus has been suggested 5; however betablockers 46-47-48, bioflavonoids and calcium channel blockers, have not shown meaningful therapeutic effects 49-50

Conflict of Interest

None declared.


1. Cansu D, Kasifoğlu T, Pasaoğlu O, Korkmaz C. Autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome) associated with cutaneous vasculitis. Joint Bone Spine. 2008 Dec;75(6):721-4. Epub 2008 Apr 15

2. Silny W, Marciniak A, Czarnecka-Operacz M, Zaba R, Schwartz RA. Gardner-Diamond syndrome.Int J Dermatol. 2010 Oct;49(10):1178-81

3. Mizutani Y, Seishima M. Autoerythrocyte sensitization syndrome with vertigo and hemilateral auditory impairment.ClinExpDermatol. 2009 Jul;34(5):e134-6

4. Puetz J, Fete T. Platelet function disorder in Gardner-Diamond syndrome: a case report and review of the literature. J PediatrHematolOncol. 2005 Jun;27(6):323-5

5. Autoerythrocyte sensitization syndrome (Gardner–Diamond syndrome): review of the literature J EurAcadDermatolVenereol. 2009 May;23(5):499-504. Epub 2009 Feb 2. Review

6. Uthman IW, Moukarbel GV, Salman SM, Salem ZM, Taher AT, Khalil IM. Autoerythrocyte sensitization (Gardner- Diamond) syndrome.Eur J Haematol. 2000 Aug;65(2):144-7. Review

7. A. Sotiriou E, Apalla Z, Apalla K, Panagiotidou D. Case report: psychogenic purpura. Psychosomatics. 2010 May;51(3):274-5

8. Mehta J, Dhurat RS, Jerajani HR, Satyapal S. Autoerythrocyte sensitization syndrome: a form of painful purpura with positive intracutaneous test. Br J Dermatol. 2004 Apr;150(4):768

9. Bostwick JM, Imig MW. Gardner-Diamond Syndrome: bruising feeling. Mayo Clin Proc. 2008 May;83(5):572

10. Bartralot, R, Gonzalez-Castro, U, Repiso, T, CastellsRodellas, A. [Autoerythrocytesensitizationsyndrome (psychogenic purpura)]. MedClin (Barc) 1995; 105:117

11. Ingber A, Alcalay J, Feuerman EJ. Autoerythrocyte sensitization (Gardner- Diamond syndrome) in men: a case report and review of the literature. Postgrad Med J. 1985 Sep;61(719):823-6 12. Klein RF, Gonen JY, Smith CM. Psychogenic purpura in a man.Psychosom Med. 1975 Jan-Feb;37(1):41-9

13. TurnerC., FreedmanM.HAutoerythrocyte sensitization syndrome in a male patient with transfusion-dependent β-thalassemia major. American Journal of PediatricHematology/Oncology 1988 10:2 (120-122)

14. RATNOFF OD. Psychogenic purpura (autoerythrocyte sensitization): an unsolved dilemma. Am J Med 1989;87:16N±21N

15. Baek JO, Jee HJ, Kim TK, Lee MG. Case of Gardner-Diamond syndrome after intramuscular stimulation. J Dermatol. 2011 Dec;38(12):1197-9

16. Kalden JR, Höffken B, Stangel W. Immune mechanism in gardner-diamond syndrome. N Engl J Med. 1977 Dec 15;297(24):1350

17. Sawhney MP, Arora G, Arora S, Prakash J. Undiagnosed purpura: a case of autoerythrocyte sensitization syndrome associated with dermatitis artefacta and pseudo-ainhum. Indian J DermatolVenereolLeprol. 2006 Sep- Oct;72(5):379-81

18. Ponizovsky AM, Barshtein G, Bergelson LD. Biochemical alterations of erythrocytes as an indicator of mental disorders: an overview. Harv Rev Psychiatry 2003;11:317e32

19. Black PH, Garbutt LD. Stress, inflammation and cardiovascular disease. J Psychosom Res 2002;52:1e23

20. Lytinas M, Kempuraj D, Huang M, et al. Acute stress results in skin corticotropinreleasing hormone secretion, mast cell activation and vascular permeability, an effect mimicked by intradermal corticotropin-releasing hormone and inhibited by histamine-1 receptor antagonists. IntArchAllergyImmunol 2003;130:224e31

21. Strunecká A, Krpejsová L, Palecek J, Mácha J, Maturová M, Rosa L, Palecková A. Transbilayer redistribution of phosphatidylserine in erythrocytes of a patient with autoerythrocyte sensitization syndrome (psychogenic purpura). Folia HaematolInt Mag KlinMorpholBlutforsch. 1990;117(6):829-41

22. Ratnoff OD. The psychogenic purpuras: a review of autoerythrocyte sensitization, autosensitization to DNA, "hysterical" and factitial bleeding, and the religious stigmata. SeminHematol. 1980 Jul;17(3):192-213

23. Brauner F, Brenner W, Gschnait F. Autosensitization to DNA. Acta DermVenereol. 1980;60(4):345-8

24. Krain LS, Levin JM, Schultz B. Decreased serum complement in the Gardner-Diamond syndrome: immunofluorescent findings and association with angioimmunoblastic lymphadenopathy. Cutis. 1978 Jan;21(1):80- 4

25. Merlen JF. [Ecchymotic patches of the fingers and Gardner-Diamond vascular purpura].Phlebologie. 1987 Apr- Jun;40(2):473-87

26. Di Grande E. Psychogenic purpura: platelet factor 3 deficiency. Arch Dermatol. 1971 Oct;104(4):444-5

27. Lotti T, Benci M, Sarti MG, Teofoli P, Senesi C, Bonan P, Ghersetich I, Panconesi E. Psychogenic purpura with abnormally increased tPA dependent cutaneous fibrinolytic activity. Int J Dermatol. 1993 Jul;32(7):521-3

28. Panconesi E, Hautmann G. Stress, stigmatization and psychosomatic purpuras.IntAngiol. 1995 Jun;14(2):130-7

29. Gundogar D, YukselBasak P, BaysalAkkaya V, Akarsu O. Autoerythrocyte sensitization syndrome associated with grief complications. J Dermatol. 2006 Mar;33(3):211-4

30. Kirschner MH, Hofmann GO, Markewitz A, Hatz R, Mempel M. Osteosynthetic reconstruction in a patient with Gardner- Diamond syndrome. J Trauma. 1995 Mar;38(3):392-5

31. Grossman RA. Autoerythrocyte sensitization worsened by a copper-containing IUD.Obstet Gynecol. 1987 Sep;70(3 Pt 2):526-8

32. Harth W, Taube KM, Gieler U. Facticious disorders in dermatology. J DtschDermatolGes. 2010 May;8(5):361-72; quiz 373. Epub 2010 Feb 12

33. Siddi GM, Montesu MA. Gardner-Diamond syndrome. J EurAcadDermatolVenereol. 2006 Jul;20(6):736-7

34. Ozyildirim I, Yücel B, Aktan M. [Psychogenic purpura with hematuria and sexual pain disorder: a case report]. Turk PsikiyatriDerg. 2010 Spring;21(1):85-9

35. Jefferson JA, Nelson PJ, Najafian B, Shankland SJ. Podocyte disorders: Core Curriculum 2011. Am J Kidney Dis. 2011 Oct;58(4):666-77

36. Gomi H, Miura T. Autoerythrocyte sensitization syndrome with thrombocytosis. Dermatology. 1994;188(2):160-2

37. Benjamin P Geisler, MDBruce J Dezube, MD.Psychogenicpurpura (Gardner-Diamond syndrome).).Ratnoff, OD. The psychogenic purpuras: a review of autoerythrocyte sensitization, autosensitization to DNA, "hysterical" and factitial bleeding, and the religious stigmata. SeminHematol 1980; 17:192

38. Behrendt C, Goos M, Thiel H, Hengge UR. [Painful bruising syndrome].Hautarzt. 2001 Jul;52(7):634-7

39. Tomec RJ, Walsh M, Garcia JC, Jordan PK. Diagnosis of autoerythrocyte sensitization syndrome in the emergency department. Ann EmergMed. 1989 Jul;18(7):780-2

40. Moll S. Unusual bleeds, unusual clots.Hamostaseologie. 2007 Aug;27(3):191- 9

41. Grace TW, Spees AJ. Gardner-Diamond syndrome. JAMA. 1981 May 15;245(19):1909

42. McIntosh RM, Ozawa T, Persoff M, Altshuler JH, Guggenheim S, Boedecker E. Nephropathy associated with Gardner- Diamond syndrome. Autologous erythrocyte antigen-antibody immune-complex disease. N Engl J Med. 1977 Jun 2;296(22):1265-7

43. Al Hawsawi K, Pope E. Pediatric psychocutaneous disorders: a review of primary psychiatric disorders with dermatologic manifestations. Am J ClinDermatol. 2011 Aug 1;12(4):247-57

44. Glowinski J, Koubi R, May V, LessanaLeibowitch M. [Gardner-Diamond syndrome in a male. Trial treatment with beta-blockers]. NouvPresse Med. 1981 Jun 27;10(28):2369-70

45. Karatosun V, Satoğlu S, Günal I, Alptekin K. Autoerythrocyte sensitization (Gardner- Diamond) syndrome mimicking compartment syndrome. Arch Orthop Trauma Surg. 2003 Sep;123(7):370-1. Epub 2003 Jun 28

46. Francisco Aomar Millán I, Pérez Fernández L, Calleja Rubio JL, Ortego Centeno N. [Autoerythrocyte sensitization purpura (Gardner-Diamond syndrome)]. Med Clin (Barc). 2008 Feb 2;130(3):120

47. Dickinson T, Malhi, S, Painter, S, et al. Association between SSRIs and upper gastrointestinal bleeding. Self-treatment with non-steroidal drugs may be confounding factor. BMJ 2000; 320:1406.

48. Glowinski J, Koubi R, May V, LessanaLeibowitch M. [Gardner-Diamond syndrome in a male. Trial treatment with beta-blockers].NouvPresse Med. 1981 Jun 27;10(28):2369-70

49. Erwin WJ, Granacher RP Jr. New behavioral data concerning the autoerythrocyte sensitization syndrome. South Med J. 1977 Jul;70(7):876-8

50. MarxG., EifrigB. Gardner-Diamond syndrome: Treatment with high-dose immunglobulin. Hamostaseologie 1992 12:4 (164-168)
Select your language of interest to view the total content in your interested language

Viewing options

Post your comment

Share This Article

Flyer image