Gardner-Diamond syndrome is a rare clinical entity characterized by the spontaneous development of bruising and subsequent skin symptoms. An autoimmune reaction to phosphatidylserine in erythrocytes triggered by significant emotional stress or physical trauma seems to be the mechanism of disease. The diagnosis is made by injection of the patient's own red blood cells into the dermis and observation of an autoimmune reaction.
Presentation
The clinical presentation of patients suffering from Gardner-Diamond syndrome (also known as autoerythrocyte sensitization syndrome) seems to start with physical trauma of the skin, seen in surgery, blunt force or accidental injuries, while emotional trauma - abortion, divorce, anxiety, etc. are also presumable triggers [1] [2]. In fact, the term psychogenic purpura is used to describe typical changes seen in this condition [1] [3]. The cause still remains undisclosed, but patients initially develop constitutional symptoms such as malaise and fatigue, followed by a burning, itching or stinging sensation, pain and induration of the skin with bruising [1] [3] [4]. As the lesions grow into pink or red plaques of various sizes and progress to bluish ecchymoses, a misdiagnosis for cellulitis or compartment syndrome is not uncommon, but spontaneous regression and complete resolution within one week and subsequent recurrence is the typical clinical course of lesions encountered in this condition [1]. Skin lesions may be encountered at any site in the body, but the most common localization are the extremities [3]. They are described in individuals of all ages, including children, and about 200 cases are documented in the literature, suggesting its very rare occurrence in medical practice [1] [3]. In addition, numerous systems may be affected, including gastrointestinal (epigastric pain, nausea, vomiting, diarrhea) and vascular (subconjunctival hemorrhage, epistaxis, hematuria, menorrhagia, bleeding from the ear canal), while glomerulonephritis, stroke, and lymphoid abnormalities are extremely rare but observed findings [1] [5]. Most common psychiatric disorders encountered in these patients include conversion symptoms, hysteria, depression, anxiety, and dissociative reactions [1] [5].
Entire Body System
- Severe Pain
This technique requires local anesthetic or ablation and is successful if at least 50% of the pain is reduced. [67] Outcome Measures There are several methods to evaluate CRPS. Each symptom has another test to evaluate its severity. [physio-pedia.com]
- Constitutional Symptom
The cause still remains undisclosed, but patients initially develop constitutional symptoms such as malaise and fatigue, followed by a burning, itching or stinging sensation, pain and induration of the skin with bruising. [symptoma.com]
Hematological
- Easy Bruising
A 34-year-old woman with a 3-year history of easy bruising of unexplained aetiology in anatomical sites consistent with self-infliction is described. Despite major surgery, the patient had never experienced inappropriate bleeding. [ncbi.nlm.nih.gov]
A 24-year-old man with a 10-year history of easy bruising of undefined aetiology in anatomical sites consistent with self-infliction is reported. [tandfonline.com]
She did not have a history of abnormal bleeding or easy bruising. There was no menorrhagia, hematuria or dysuria. Recent wisdom teeth extraction was not complicated by excessive bleeding. [academic.oup.com]
However, the typical bleeding pattern in vitamin C deficiency is perifollicular hemorrhage and gum bleeding; vitamin K deficiency may cause a range of findings from easy bruising to more severe bleeding. (See "Healthy diet in adults".) [medilib.ir]
- Subcutaneous Bleeding
Rowell A painful bleeding syndrome associated with increased fibrinolytic activity Br J Dermatol, 91 (1974), pp. 591-596 [12] E. Panconesi, G. [elsevier.es]
Gastrointestinal
- Abdominal Pain
[…] deep under the skin at a particular site abdominal pain and nausea emesis and lost of appetite headaches Treatment The pain required narcotics, which are delivered by patient-controlled analgesia because oral and intravenous analgesia administered as [checkorphan.org]
pain with her episodes of purpura. [ijdvl.com]
As the bruises developed, the patient continued to complain of abdominal pain and nausea. She also developed emesis and lost her appetite. [academic.oup.com]
Associated symptoms include abdominal pain, nausea, vomiting, diarrhea, and headache. Prodromal symptoms such as pain, warmth, or itching at the site prior to the bruising have been described. The bruises resolve in approximately 2 weeks but recur. [visualdx.com]
- Diarrhea
In addition, numerous systems may be affected, including gastrointestinal (epigastric pain, nausea, vomiting, diarrhea) and vascular (subconjunctival hemorrhage, epistaxis, hematuria, menorrhagia, bleeding from the ear canal), while glomerulonephritis [symptoma.com]
Associated symptoms include abdominal pain, nausea, vomiting, diarrhea, and headache. Prodromal symptoms such as pain, warmth, or itching at the site prior to the bruising have been described. The bruises resolve in approximately 2 weeks but recur. [visualdx.com]
[…] patients, particularly if both lower extremities are affected. 58,99 Gastrointestinal System In a prospective study of 270 CRPS patients, the most common gastrointestinal (GI) symptoms were constipation (41%), nausea (23.3%), vomiting (11.5%), intermittent diarrhea [practicalpainmanagement.com]
It should be noted that some patients do not demonstrate any predominant psychopathological syndrome. 1,3 Besides the psychogenic and cutaneous symptoms, systemic symptoms may occur, such as gastrointestinal symptoms (abdominal pain, diarrhea, nausea [elsevier.es]
Cardiovascular
- Vascular Disease
[…] system and retinal vascular disease Genetic central nervous system malformation Genetic cerebellar malformation Genetic cerebral malformation Genetic cerebral small vessel disease Genetic chronic primary adrenal insufficiency Genetic complex vascular [orpha.net]
Skin
- Purpura
A form of purpura producing painful bruising following autosensitization to red blood cells in certain women. Blood. 1955;10:675-90. Ratnoff OD. Psychogenic purpura (autoerythrocyte sensitization): an unsolved dilemma. Am J Med. 1989;87:16-21. [ijmedicine.com]
REFERENCES Ratnoff OD Psychogenic purpura (authoerythrocyte sensitization): an unsolved dilemma. [mayoclinicproceedings.org]
Lababidi Z, Friedman R (1971) Psychosomatic purpura. Mo Med 68:386–388 PubMed Google Scholar 11. [link.springer.com]
Abstract The case of a patient with two unusual dermatologic entities, multiple glomus tumors and the painful purpura of Gardner-Diamond syndrome, is reported. [ncbi.nlm.nih.gov]
- Dermatitis
In view of the above, a suspicion of AES with dermatitis artefacta was entertained. [ijdvl.com]
García Bravo, Dermatitis artefacta: revisión, Actas Dermo-Sifiliográficas, 104, 10, (854), (2013). A. Rodríguez Pichardo and B. García Bravo, Dermatitis Artefacta: A Review, Actas Dermo-Sifiliográficas (English Edition), 104, 10, (854), (2013). [doi.org]
[…] bacterial and fungal infections, psoriasis, contact dermatitis, and much more. [books.google.com]
Dermatitis artefacta Dermatitis artefacta (also known as factitial dermatitis or pathomimia) is characterized by self-inflicted skin lesions that raise suspicion because of their curious morphology, localization, lack of therapeutic response, and long [dovepress.com]
- Skin Disease
disease Photosensitization Vascular disorders of the skin Keyword (es) Eritrocito Simulacion Piel patologia Fotosensibilizacion Vaso sanguineo piel patologia Classification Pascal 002 Biological and medical sciences / 002B Medical sciences / 002B08 Dermatology [pascal-francis.inist.fr]
A thousand full-color photographs help you to recognize the characteristic manifestations of every type of skin disease. Hurwitz remains the indispensable pediatric dermatology resource you need for optimal practice. [books.google.com]
W Chen, M Mempel, C Traidl‐Hofmann, S Al Khusaei and J Ring, Gender aspects in skin diseases, Journal of the European Academy of Dermatology and Venereology, 24, 12, (1378-1385), (2010). [doi.org]
It is of paramount importance for the clinician to establish an appropriate physician-patient-family relationship in order to diagnose and treat factitial skin diseases. [dovepress.com]
- Sweating
[…] abnormalities are reported in approximately 30% of patients during the course of the illness. 95 Denervated or abnormal sweat glands were seen in autopsies reviewed by Oaklander et al. 3 Sweat glands may respond to circulating norepinephrine, although [practicalpainmanagement.com]
Q-sweat is an adequate instrument to measure sweat production. [physio-pedia.com]
[…] palate-lateral synechia syndrome Cleidorhizomelic Syndrome CLOVES syndrome COACH Syndrome Cockayne syndrome + cocoon syndrome CODAS Syndrome Coffin-Lowry syndrome Coffin-Siris syndrome + Cogan syndrome + Cohen Syndrome Cohen-Gibson Syndrome cold-induced sweating [rgd.mcw.edu]
Other reports include wounds to the forehead ("crown of thorns"), tears of blood or sweating blood, wounds to the back as from whipping, or wounds to the shoulder as from bearing a cross [30]. [medilib.ir]
Face, Head & Neck
- Epistaxis
However there was no history of epistaxis, hemoptysis, hematuria or blood in stool. In view of the above, a suspicion of AES with dermatitis artefacta was entertained. [ijdvl.com]
Accompanying features may include fever, arthralgia, myalgia, headache, gastrointestinal problems, or hematuria and epistaxis, among others. The disease occurs predominantly in women. [findexpertmd.com]
In addition, numerous systems may be affected, including gastrointestinal (epigastric pain, nausea, vomiting, diarrhea) and vascular (subconjunctival hemorrhage, epistaxis, hematuria, menorrhagia, bleeding from the ear canal), while glomerulonephritis [symptoma.com]
There was no history of epistaxis or menorrhagia. No physical trauma or drug usage was described. [jpedres.org]
Neurologic
- Headache
[…] includes the symptoms listed below: localized tingling localized burning skin hemorrhage bruises progressively enlarged bruises sensation of pain and warmth deep under the skin at a particular site abdominal pain and nausea emesis and lost of appetite headaches [checkorphan.org]
There are many examples of unexplained medical symptoms, such as recurrent abdominal pain of childhood and headaches – often described as ‘the diagnosis of exclusion’. [academic.oup.com]
Twitter Instagram YouTube LinkedIn Search Home Specialties Topics Multimedia Current Issue Learning/CME Learning/CME CME Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk Case 36-2022: A 30-Year-Old Woman with Decreased Vision and Headache [nejm.org]
The associated complaints in such patients include neurological and ocular symptoms, hemorrhagic manifestations, menorrhagia and a varied symptomatology.[6],[7] Our patient had transient headaches, muscular and joint aches and occasional chest and abdominal [ijdvl.com]
- Complex Regional Pain Syndrome Type II
Definition/Description Complex regional pain syndrome (CRPS) is a term for a variety of clinical conditions characterised by chronic persistent pain and are subdivided into Type I and Type II CRPS. [physio-pedia.com]
- Polyneuropathy
Pituitary Stalk Interruption Syndrome Piussan Lenaerts Mathieu syndrome Plica syndrome Plummer-Vinson Syndrome Podder-Tolmie Syndrome POEMS syndrome Pointer Syndrome Poland syndrome polycystic ovary syndrome + Polydactyly Myopia Syndrome Polyendocrine-Polyneuropathy [rgd.mcw.edu]
Workup
To make the diagnosis, it is necessary to conduct a thorough clinical and laboratory workup that will exclude other more common conditions presenting with similar symptoms. Firstly, a detailed patient history is necessary, which will identify information regarding the onset and duration of symptoms, family history of bleeding disorders and detection of possible events that induce a significant amount of stress [1]. A meticulous physical examination should follow, and complete inspection of the skin can reveal numerous ecchymoses (either resolving or evolving) on different parts of the body [1]. Additionally, exclusion of puncture wounds (seen in IV drug users) as the cause of skin lesions must be made [1] [3] [4]. Laboratory workup with levels of hemoglobin, hematocrit, platelet count and erythrocyte sedimentation rate within physiological levels, while prothrombin time, activated partial thromboplastin time, as well as inflammatory markers, serum electrolytes, and specific coagulation factors will also be normal [2]. These findings will exclude many important disorders (disseminated intravascular coagulation, Henoch-Schonlein purpura, von Willebrand disease, systemic lupus erythematosus, infection, etc.) but a definite diagnosis can be obtained by injecting patient's own washed erythrocytes into the dermis, and a subsequent autoimmune reaction (to phosphatidylserine in their stroma) will cause bruising [1] [2]. In addition, histopathological analysis can be performed by obtaining a sample of tissue. Extravasation of blood cells, as well as the absence of inflammatory or infectious components, is always encountered [1] [3].
Other Pathologies
- Lymphocytic Infiltrate
Punch biopsies of the skin lesions revealed scant superficial perivenular lymphocytic infiltration. [apallergy.org]
A skin biopsy of the bruise showed nonspecific lymphocytic infiltration and hemorrhage. There was no evidence of vasculitis, and immunofluorescence studies were negative. An upper endoscopy demonstrated esophagitis, but was otherwise normal. [academic.oup.com]
Biopsies have shown intradermal hemorrhage and various degrees of edema with scant perivascular lymphocytic infiltrates [7]. In the Mayo Clinic series, 28 individuals underwent skin biopsy [1]. [medilib.ir]
Treatment
Due to the rare nature of this disorder, there exist few guidelines for prompt clinical diagnosis and optimal treatment. [alliedacademies.org]
Although our treatment could be described as ‘symptomatic’ or ‘supportive’ (total parenteral nutrition, narcotic analgesia), these treatments are not without side effects themselves. [academic.oup.com]
Dermatological signs identical to Gardner-Diamond syndrome should alert the physician to avoid unnecessary fasciotomy, as these patients respond well to psychiatric treatment as in the present case. [ncbi.nlm.nih.gov]
There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]
Treatment Options No controlled studies exist. Treatment should be directed toward lesion control, pain control, and intervention for an underlying or associated psychiatric disorder. [dermatologyadvisor.com]
Prognosis
Prognosis - Gardner-Diamond Syndrome Not supplied. [checkorphan.org]
The prognosis of AES syndrome is good; no fatalities have been reported secondary to the disease. However, the lesions have recurred for as long as 30-40 years. [apallergy.org]
The long-term prognosis depends on the age of diagnosis and the symptoms experienced. Is there a cure for Gardner syndrome? No. There is no known cure for Gardner syndrome. [my.clevelandclinic.org]
Although there is no specific treatment, the prognosis of DGS is good, most cases experience recurrent lesions that appear in times of increased stress, but mortality due to the syndrome is not reported. [jpedres.org]
Optimal Therapeutic Approach for this Disease Once confident in the diagnosis, reassure the patient that the prognosis is good. Explain that most will have remission of symptoms (except possible recurrences during stressful periods). [dermatologyadvisor.com]
Etiology
The exact etiology of the syndrome is an enigma even today, since its first description in 1955.[1] We describe this rare condition in a young woman with an onset in her early teens, who was subjected to extensive investigations over a period of nine [ijdvl.com]
Etiology The etiology is unclear. Stress and psychiatric disorders frequently are present; possibly etiologic. [dermatologyadvisor.com]
Owing to the uncertain etiology, we suggest that the functional platelet defect found may intervene, maintaining and making the ecchymotic lesions worse. [ncbi.nlm.nih.gov]
Subsequent investigations failed to elucidate an organic etiology. [academic.oup.com]
Epidemiology
(level of evidence 2B) ↑ ALLEN, G., et al., Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients. Pain,1999. [physio-pedia.com]
(See 'Epidemiology' above.) ●Presentation – There is no typical or classic presentation but there is often a triggering event (surgery, trauma, emotional stress, abuse). [medilib.ir]
The prevailing psychiatric disorders were depression, sexual difficulties, and obsessive-compulsive disorders. 14 EPIDEMIOLOGY As mentioned before, it is a rare entity from which we have little accurate statistic data. [internalmedicine.imedpub.com]
[…] syndrome. [7] Etiology The causes of FAP are as follows: Mutation of APC, located on chromosome 5 Loss of DNA methylation Mutation of RAS, located on chromosome 12 Deletion of DCC, located on chromosome 18 Mutation of TP53, located on chromosome 17 Epidemiology [emedicine.medscape.com]
Pathophysiology
The etiology and pathophysiology of this syndrome are poorly understood, but the lesions are likely self-induced. The syndrome typically occurs in white women who are experiencing emotional stress or who have concomitant psychiatric illness. [msdmanuals.com]
The pathophysiology of the disease is not fully understood, and little is known about management modalities for this syndrome. [read.qxmd.com]
Additional associated findings, including myalgias, headaches, and bleeding have been reported.4 To date, many possible pathophysiological mechanisms of GDS have been proposed. [jcadonline.com]
Although the pathophysiology of GDS is elusive, hematologic, dermatological, neurologic, and psychiatric components will likely factor in ultimate explanations. [mayoclinicproceedings.org]
Prevention
Prevention - Gardner-Diamond Syndrome Not supplied. Diagnosis - Gardner-Diamond Syndrome Not supplied. Prognosis - Gardner-Diamond Syndrome Not supplied. [checkorphan.org]
Prevention How can I reduce my risk for Gardner syndrome? Because Gardner syndrome is an inherited condition, there is no known way to prevent it from occurring altogether. [my.clevelandclinic.org]
Improvement Performance Measures Perioperative Care and Consultation Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics Pharmacy and Clinical Pharmacology Physical Medicine and Rehabilitation Physical Therapy Physician Leadership Poetry Population Health Preventive [jamanetwork.com]
We postulate that, without any specific therapy, just knowing the diagnosis and explaining about the nature of the disease could be helpful to the patient to prevent recurrent episodes. [e-ijd.org]
References
- Jafferany M, Bhattacharya G. Psychogenic Purpura (Gardner-Diamond Syndrome). Prim Care Companion CNS Disord. 2015;17(1):10.4088/PCC.14br01697.
- Zhao H, Luo F, Li H. Autoerythrocyte Sensitization Syndrome Presenting with General Neurodermatitis: Factitious Purpura or Psychophysiological Entity? Dermatol Ther (Heidelb). 2012;2(1):5
- Meeder R, Bannister S. Gardner-Diamond syndrome: Difficulties in the management of patients with unexplained medical symptoms. Paediatr Child Health. 2006;11(7):416-419.
- Okur M, Turan H, Özkan A, Güneş C, Kocabay K. An Extremely Rare Cause of Bruising in Children: Autoerythrocyte Sensitization Syndrome. Turk J Haematol. 2012;29(2):201-203.
- Sarkar S, Ghosh SK, Bandyopadhyay D, Nath S. Psychogenic purpura. Indian J Psychiatry. 2013;55(2):192-194.