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INTRODUCTION

Establishing a correct diagnosis of COPD is important because appropriate management can decrease symptoms (especially dyspnea), reduce the frequency and severity of exacerbations, improve health status, improve exercise capacity, and prolong survival [ 9 ]. Many health conditions in older adults can result in dyspnea or cough, so respiratory symptoms should not be attributed to COPD without appropriate evaluation and diagnosis.

The definition, clinical manifestations, diagnostic evaluation, and staging of COPD are discussed here. The risk factors, natural history, prognosis, and treatment of COPD are discussed separately.

● (See "Chronic obstructive pulmonary disease: Risk factors and risk reduction" .)

● (See "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions" .)

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• Review Article
• Published: 25 July 2023

Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update

• Sizhen Su 1 ,
• Yimiao Zhao 2 , 3 ,
• Na Zeng 2 , 3 ,
• Xiaoxing Liu 1 ,
• Yongbo Zheng 4 ,
• Jie Sun 5 ,
• Yi Zhong 1 ,
• Shuilin Wu 2 , 3 ,
• Shuyu Ni 2 , 3 ,
• Yimiao Gong 1 , 4 ,
• Zhibo Zhang 1 ,
• Nan Gao 6 ,
• Kai Yuan   ORCID: orcid.org/0000-0002-3498-8163 1 ,
• Wei Yan   ORCID: orcid.org/0000-0002-5866-6230 1 ,
• Le Shi   ORCID: orcid.org/0000-0003-4750-3492 1 ,
• Arun V. Ravindran 7 ,
• Thomas Kosten   ORCID: orcid.org/0000-0003-1505-555X 8 ,
• Jie Shi   ORCID: orcid.org/0000-0001-6567-8160 2 ,
• Yanping Bao   ORCID: orcid.org/0000-0002-1881-0939 2 , 3 &
• Lin Lu   ORCID: orcid.org/0000-0003-0742-9072 1 , 2 , 4  

Molecular Psychiatry volume  28 ,  pages 4056–4069 ( 2023 ) Cite this article

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The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.

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The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Post-acute COVID-19 syndrome

A COVID-19 pandemic guideline in evidence-based medicine

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Acknowledgements

This study was supported by a grant from the National Key Research and Development Program of China (2021YFC0863700, 2019YFA0706200), Natural Science Foundation of Beijing Municipality of China (M23013), National Programs for Brain Science and Brain-like Intelligence Technology of China (STI2030-Major Projects, 2021ZD0200800, 2021ZD0200700), and the National Natural Science Foundation of China (no. 82288101, 82171514). The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interests.

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Sizhen Su, Xiaoxing Liu, Yi Zhong, Yimiao Gong, Zhibo Zhang, Kai Yuan, Wei Yan, Le Shi & Lin Lu

National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China

Yimiao Zhao, Na Zeng, Shuilin Wu, Shuyu Ni, Jie Shi, Yanping Bao & Lin Lu

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LL and YB proposed the topic and main idea, SS was responsible for literature search, drafting the manuscript, and making the figures, and revising all versions. XL, NZ, YZ, YZ, SW, YZ, JS, and SN contributed to the first draft. YG, ZZ, NG, KY, WY, LS, AVR, TK, and JS revised the manuscript for intellectual content. YB and LL proposed the topic of the review and commented on and revised the manuscript.

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Su, S., Zhao, Y., Zeng, N. et al. Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update. Mol Psychiatry 28 , 4056–4069 (2023). https://doi.org/10.1038/s41380-023-02171-3

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Poliomyelitis: Clinical Presentation

Updated August 10, 2022

• Infection and Transmission
• Post-polio Syndrome
• Diagnosis and Laboratory Testing
• Reporting Suspected Cases of Polio

In July 2022, CDC was notified of a case of polio in an unvaccinated individual from Rockland County, New York, caused by vaccine-derived poliovirus type 2 . CDC is consulting with the New York State Department of Health on their investigation. This does not change CDC recommendations for polio vaccination. CDC urges everyone who is not fully vaccinated to complete the polio vaccination series as soon as possible. Small updates were made on these pages to emphasize vaccination recommendations for adults, clarify next steps when suspecting a case of polio, and update references.

Although poliovirus is no longer endemic in the United States, it’s important that healthcare professionals  rule out poliovirus infection  in cases of unexplained  acute flaccid paralysis (AFP) that are clinically compatible with polio, particularly those with anterior myelitis, to ensure that any importation of poliovirus is quickly identified and investigated. See the MMWR case study on AFP  for more information.

There has not been a case of wild polio acquired in the United States since 1979. The last imported case of wild polio was in 1993. However, poliovirus infections still occur  in some countries and could easily be brought into the United States. In the last decade, many polio-free countries have had cases of polio imported through international travel.

Transmission electron micrograph (TEM) of poliovirus type 1.

Poliovirus is a member of the  Enterovirus  genus, family  Picornaviridae . Enteroviruses are transient inhabitants of the gastrointestinal tract and are stable at acidic pH. Picornaviruses are small, ether-insensitive viruses with an RNA genome. Poliovirus is highly contagious and causes polio, or poliomyelitis, a serious and debilitating disease.

There are three poliovirus serotypes (PV1, PV2, and PV3) with minimal heterotypic immunity between them. That is, immunity to one serotype does not produce significant immunity to the other serotypes.

Poliovirus infects only humans. Infection is more common in infants and young children. Polio occurs at an earlier age among children living in poor hygienic conditions. In temperate climates, poliovirus infections are most common during summer and autumn. In tropical areas, the seasonal pattern is less pronounced.

The virus enters through the mouth and multiplies in the oropharynx and gastrointestinal tract. The virus is usually present in nasopharyngeal secretions for 1 to 2 weeks and can be shed in stools for several weeks after infection, even in individuals with minor symptoms or no illness. 

Most people infected with poliovirus will not have any visible symptoms. About one out of four people will have flu-like symptoms. These symptoms usually last 2 to 5 days, then go away on their own.

Fewer than 1% of people will have weakness or paralysis in their arms, legs, or both. The paralysis can lead to permanent disability and death.

The poliovirus incubation period for nonparalytic symptoms is 3 to 6 days. The onset of paralysis usually occurs 7 to 21 days after infection.

Polio vaccine provides the best protection against polio.

CDC recommends that children and adults who are unvaccinated or incompletely vaccinated get polio vaccine to protect against polio, or poliomyelitis.

For specific vaccination recommendations visit: Polio Vaccination: For Healthcare Providers .

Adults who had paralytic poliomyelitis during childhood may develop  noninfectious post-polio syndrome (PPS)  15 to 40 years later. PPS is characterized by slow and irreversible exacerbation of weakness often in those muscle groups involved during the original infection. Muscle and joint pain also are common manifestations. The prevalence and incidence of PPS is unclear. Studies estimate that 25–40% of polio survivors suffer from PPS.

Acute flaccid paralysis (AFP) is a manifestation of a wide spectrum of clinical diseases. Worldwide, children younger than 15 years are the age group at highest risk of developing polio and some other forms of AFP. Even in the absence of laboratory-documented poliovirus infection, AFP is expected to occur at a rate of at least 1 per 100,000 children annually. It can result from a variety of infectious and noninfectious causes. Known viral causes of AFP include enterovirus, adenovirus, and West Nile virus. However, AFP caused by these agents is very uncommon in the United States. A study examining AFP in 245 children younger than 15 years in California from 1992-1998 found the most common diagnoses were Guillain-Barré Syndrome (23%), unspecified AFP (21%), and botulism (12%).

Polio Case Definition and Diagnosis

A  probable case of polio  is defined as an acute onset of flaccid paralysis of one or more limbs with decreased or absent tendon reflexes in the affected limbs, without other apparent cause, and without sensory or cognitive loss.

Paralysis usually begins in the arm or leg on one side of the body (asymmetric) and then moves towards the end of the arm or leg (progresses to involve distal muscle groups). This is described as descending paralysis. Many patients with AFP will have a lumbar puncture and analysis of cerebrospinal fluid (CSF) performed as part of their evaluation. Detection of poliovirus in CSF from confirmed polio cases is uncommon, and a negative CSF test result cannot be used to rule out polio.

Consider polio in patients with polio-like symptoms, especially if the person is unvaccinated, incompletely vaccinated, recently traveled abroad to a place where polio still occurs, or was exposed to a person who recently traveled to one of these areas. Only healthcare workers with evidence of complete polio vaccination should attend to the patient.

If you suspect polio:

• Practice good hand hygiene and contact precautions when interacting with the patient.
• Evaluate the patient for flaccid weakness and document tone, reflexes, and muscle strength.
• Poliomyelitis has been classified as immediately notifiable, extremely urgent. Contact the state or local health department immediately to report a patient with suspected poliomyelitis.
• Collect appropriate stools (whole stool) and throat specimens (OP swab): 2 specimens of each taken at least 24 hours apart during the first 14 days after onset of paralytic disease.
• Store specimens at –20 degrees celsius and ship frozen.
• For questions, contact the CDC Emergency Operations Center at 770-488-7100.

The rapid investigation of suspected polio cases is critical to identifying possible poliovirus transmission and implementing proper control measures. For more information see CDC poliomyelitis guidelines  for epidemiologic, clinical, and laboratory investigations of AFP to rule out poliovirus infection.

Paralytic polio  has been classified as  “Immediately notifiable, Extremely Urgent,”  which requires that local and state health departments contact CDC  within 4 hours .

Non-paralytic polio  has been classified as  “Immediately notifiable, Urgent,”  which requires that local and state health departments contact CDC  within 24 hours .

CDC (Emergency Operations Center, 770-488-7100) will provide consultation regarding:

• The collection of appropriate clinical specimens needed for poliovirus detection
• The initiation of appropriate consultations and procedures to rule out or confirm poliomyelitis
• The compilation of medical records

For more information about what should be collected as part of a case investigation see:

• Polio – Vaccine Preventable Diseases Surveillance Manual
• Suspected Polio Case Worksheet [PDF – 95KB]

Each state and territory has regulations or laws governing the reporting of diseases and conditions of public health importance. These regulations and laws list the diseases to be reported and describe those persons or groups responsible for reporting such as healthcare providers, hospitals, laboratories, schools, daycare and childcare facilities, and other institutions. Contact your state health department for reporting requirements in your state.

• Progress Toward Polio Eradication — Worldwide, January 2020–April 2022
• Guidance for Assessment of Poliovirus Vaccination Status and Vaccination of Children Who Have Received Poliovirus Vaccine Outside the United States
• Paralytic syndromes in children: epidemiology and relationship to vaccination.
• Acute Flaccid Paralysis with Anterior Myelitis — California, June 2012–June 2014
• Zangwill KM, Yeh SH, Wong EJ, Marcy SM, Eriksen E, Huff KR, et al. Paralytic syndromes in children: epidemiology and relationship to vaccination.  Pediatr Neurol . 2010;42(3):206-12.

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• Polio Vaccination
• Polio Overview for Travelers

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Manifestations of Infection

Manifestations of infection may be local (eg, cellulitis, abscess) or systemic (most often fever ). Manifestations may develop in multiple organ systems. Severe, generalized infections may have life-threatening manifestations (eg, sepsis and septic shock ). Most manifestations resolve with successful treatment of the underlying infection.

Most infections increase the pulse rate and body temperature, but others (eg, typhoid fever, tularemia, brucellosis, dengue) may not elevate the pulse rate commensurate with the degree of fever (relative bradycardia). Hypotension can result from hypovolemia, septic shock, or toxic shock . Hyperventilation and respiratory alkalosis are common.

Alterations in sensorium (encephalopathy) may occur in severe infection regardless of whether central nervous system infection is present. Encephalopathy is most common and serious in older adults and may cause anxiety, confusion, delirium, stupor, seizures, and coma.

Hematologic

Infectious diseases commonly increase the numbers of mature and immature circulating neutrophils. Mechanisms include demargination and release of immature granulocytes from bone marrow, interleukin-1– and interleukin-6–mediated release of neutrophils from bone marrow, and colony-stimulating factors elaborated by macrophages, lymphocytes, and other tissues. Exaggeration of these phenomena (eg, in trauma, inflammation, and similar stresses) can result in release of excessive numbers of immature leukocytes into the circulation (leukemoid reaction), with leukocyte counts up to 25,000 to 30,000/mcL (25 to 30 × 10 9 /L).

Conversely, some infections (eg, typhoid fever, brucellosis) commonly cause leukopenia. In overwhelming, severe infections, profound leukopenia is often a poor prognostic sign.

Characteristic morphologic changes in the neutrophils of septic patients include Döhle bodies, toxic granulations, and vacuolization.

Anemia can develop despite adequate tissue iron stores. If anemia is chronic, it is a normochromic, normocytic anemia characterized by low serum iron, low total iron-binding capacity, and normal to increased serum ferritin.

Serious infection may cause thrombocytopenia and disseminated intravascular coagulation (DIC).

Other organ systems

Pulmonary compliance may decrease, progressing to acute respiratory distress syndrome (ARDS) and respiratory muscle failure.

Renal manifestations range from minimal proteinuria to acute renal failure , which can result from shock and acute tubular necrosis, glomerulonephritis, or tubulointerstitial disease.

Hepatic dysfunction, including cholestatic jaundice (often a poor prognostic sign) or hepatocellular dysfunction, occurs with many infections, even though the infection does not localize to the liver.

Gastrointestinal (GI) manifestations include upper GI bleeding due to stress ulceration that may occur during sepsis.

Endocrinologic dysfunctions include

Increased production of thyroid-stimulating hormone, vasopressin , insulin , and glucagon

Breakdown of skeletal muscle proteins and muscle wasting secondary to increased metabolic demands

Bone demineralization

Hypoglycemia occurs infrequently in sepsis, but adrenal insufficiency should be considered in patients with hypoglycemia and sepsis. Hyperglycemia may be an early sign of infection in diabetics.

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• Celiac Disease

Definition and Clinical Manifestations

• Pathogenesis
• Epidemiology
• Special Issues (FAQs)
• Associated Disorder

Gluten is the term for a protein component of wheat and similar proteins found in rye and barley. In people with celiac disease, the body mounts an immune reaction to gluten. The immune system goes on high alert. It attacks and damages the small intestine. The nature of this immune response is not an allergic reaction but a delayed type immune response.

A Quick Tour of The Small Intestine

Normal small intestine

In digesting the foods we eat, it’s the small intestine that does the “heavy lifting.” This organ performs the major work of breaking the food (nutrients) down into smaller fragments or components in a process that is called digestion. These components are then absorbed by the small intestine. They include protein, carbohydrate, fats, minerals and vitamins. They are then released into the bloodstream which carries them to all the tissues and cells of the body. This process of digestion, absorption and release into the circulation involves the normal functioning of the stomach, small intestine, pancreas and liver.

Critical to this process are tiny filaments called villi, which line the small intestine. These microscopic finger-like projections greatly expand the intestine’s surface area, maximizing the effective absorption of nutrients into the bloodstream. When the immune system of an individual with celiac disease goes into overdrive, it attacks and destroys intestinal villi (atrophy). Nutrients cannot be fully absorbed. This results in the term malabsorption. In celiac disease, all the components of the diet (carbohydrate, fats, minerals and vitamins) may be malabsorbed, or only a single nutrient such as a mineral (calcium or iron) or a single vitamin such as folic acid. The ability to take full nourishment from food is compromised.

The immune response in the intestine as well as causing atrophy of villi results in a marked inflammatory response and the generation of antibodies to food components (anti-gliadin antibodies and auto antibodies) tissue transglutaminase and endomysial antibodies. These antibodies while not causing any damage reflect the autoimmune nature of celiac disease and are used as diagnostic tests. This marked inflammatory response may be manifested as generalized systemic symptoms while the autoantibodies may be responsible or contribute to other organ damage and symptoms. In celiac disease, this systemic inflammatory response and multiple other organ involvement marks celiac disease as a multisystem disease. In fact, celiac disease more resembles a multisystem disorder with the possibility of every organ in the body being affected. Patients therefore may present with symptoms related to inflammation and malabsorption (diarrhea, abdominal pain and weight loss). Patients may present with manifestations of malabsorption of nutrients such as anemia due to iron deficiency or osteoporosis due to calcium and vitamin D malabsorption. Whereas the skin problem, dermatitis herpetiformis (DH), reflects a systemic antibody response to tissue transglutaminase generated in the intestine but manifested in the skin by these antibodies reacting with tissue transglutaminase present in the skin. Other organ involvement may be the result of nutritional deficiency, antibody directed inflammation as part as an autoimmune response.

And once in attack mode, the immune system doesn’t always stop with the small intestine, but may also damage other organs.

Modes of Presentation of Celiac Disease

The classification of the main modes of presentation of adults with celiac disease into “classical” – diarrhea predominant and “silent” is widely accepted. The silent group includes atypical presentations and those presenting with complications of celiac disease as well as truly asymptomatic individuals picked up through screening high risk groups.

Presentation in Children

Children with untreated celiac disease are at special risk. Malnutrition during this period can have significant effects on growth and development. Failure to thrive in infants, learning difficulties in school-age children, irritability and behavioral difficulties, delayed puberty, and short stature as well as recurrent abdominal pain and constipation are all common symptoms of celiac disease.

Presentation in Adults

In order to assess the clinical spectrum of celiac disease in the United States, we obtained data on 1138 people with biopsy proven celiac disease. Our results demonstrated that the majority of individuals were diagnosed in their 4th to 6th decades. Females predominated (2.9:1); however the female predominance was less marked in the elderly. Diarrhea was the main mode of presentation, occurring in 85%. Most strikingly, symptoms were present a mean of 11 years prior to diagnosis.

In order to assess whether the presentation had changed over time we analyzed the mode of presentation for a series of patients seen in the Celiac Center at Columbia University in New York.4 There were 227 patients with biopsy proven celiac disease. We noted that females again predominated, in a ratio of 1.7 to 1. Mean age at diagnosis was 46.4 ± 1.0 years (range 16 to 82 years) and was similar in men and women. Females were younger and had a longer duration of symptoms compared to the males. Diarrhea was the main mode of presentation (in 62%) with the remainder classified as silent (38%). This later group included anemia or reduced bone density as presentations (15%), screening first-degree relatives (13%), and incidental diagnosis at endoscopy performed for such indications as reflux or dyspepsia (8%). We compared those diagnosed before and after 1993, (when serologic testing was first seen in patients), and noted a reduction in those presenting with diarrhea, 73% versus 43% (p=0.0001) and a reduction in the duration of symptoms, from 9.0 ± 1.1 years to 4.4 ± 0.6 years (p<0001). These results suggested that the use of serologic testing was responsible for more patients being detected with celiac disease having presented in non-classical ways, after a shorter duration of symptoms. Further analysis of the patients seen at the Celiac Disease Center at Columbia University has revealed that progressively fewer patients are presenting with diarrhea, less than 50% of those diagnosed in the last 10 years.

Many patients with celiac disease, 36% in our series and 29% of Canadians with celiac disease, have had a previous diagnosis of irritable bowel syndrome. In fact, screening of patients seen in irritable bowel referral clinics in England and Iran reveals celiac disease in a significant number of patients. The majority of patients with celiac disease, detected in a primary care screening study had symptoms attributable to an irritable bowel syndrome.

Iron Deficiency Anemia

Iron deficiency anemia was the mode of presentation in 8% of the individuals seen by us, 4 and was reported as a prior diagnosis in 40% of Canadians with celiac disease. In a study from the Mayo Clinic, celiac disease was identified as the cause of iron deficiency in 15% of those undergoing endoscopic assessment for iron deficiency. While in a prospective study of adults, mean age in their 50’s, Karnum et al found 2.8% to have celiac disease. Anemia in celiac disease is typically due to iron deficiency, though vitamin B12 and folic acid deficiency may also be present and contribute to anemia.

Osteoporosis

A diagnosis of celiac disease may be made during the evaluation of reduced bone density (osteopenia or osteoporosis). In our study reduced bone density was more severe in men than women. Certainly men and premenopausal women with osteoporosis should be evaluated for celiac disease even if they lack evidence of calcium malabsorption, though the yield in menopausal women is low.

Incidental Recognition at Endoscopy for Reflux

An increasingly important mode of presentation is the recognition of endoscopic signs of villous atrophy in individuals who undergo endoscopy for symptoms not typically associated with celiac disease. These endoscopic signs include reduction in duodenal folds, scalloping of folds and the presence of mucosal fissures. The indications for upper gastrointestinal symptoms include dyspepsia, upper abdominal pain or gastroesophageal reflux. This presentation accounted for 10% of those who were diagnosed with celiac disease in our series. Interestingly symptoms of gastroesophageal reflux may resolve after starting a gluten-free diet. This is thought to be due to resolution of an accompanying motility disorder. These endoscopic abnormalities of the duodenal mucosa are not specific nor sensitive markers of celiac disease.

There is an argument for the routine biopsy of the duodenum in anyone undergoing upper gastrointestinal endoscopy to detect celiac disease, irrespective of the appearance of the duodenal mucosa.

Screening of high risk groups is, especially relatives of patients with celiac disease is a major mode of presentation. Studies reveal that 5% to 10% of first degree relatives of patients with celiac disease have serologic and biopsy evidence of the disease. A single testing of relatives does not suffice to detect all those with celiac disease. For those initially negative by screening antibodies, 3.5% will become positive a mean of 2 years after their initial testing. Other groups that are frequently screened for celiac disease include those with Type 1 diabetes, Down syndrome, and primary biliary cirrhosis.

Atypical Presentations

Among the atypical presentations that we have encountered are neurologic problems. We have found that 8% of those attending a peripheral neuropathy center, for evaluation of peripheral neuropathy, had celiac disease. The neuropathy is typically sensory in type, involving the limbs and sometimes the face. Nerve conduction studies are frequently normal; however skin biopsies reveal nerve damage in small fibers. We have also identified patients with severe ataxia. We have not identified patients with epilepsy, a neurologic manifestation that may be more common in childhood celiac disease.

Other, less common presentations, are abnormalities of blood chemistry determinations such as elevated serum amylase, secondary to macroamylasemia, hypoalbuminemia, hypocalcemia, vitamin deficiency states, and evidence of hyposplenism. We have seen patients referred because of dental enamel defects. Many females diagnosed with celiac disease have a history of infertility and there is a yield of screening infertile individuals for celiac disease.

Dermatitis Herpetiformis

Many people with gluten intolerance experience symptoms mainly as Dermatitis Herpetiformis (DH), a chronic disease of the skin. Patches of intensely itchy raised spots appear on the body, often symmetrically, on both elbows or both buttocks for example. However, it can occur anywhere on the body. It may occur on the face or in the hair, especially along the hairline. In this case, the immune system’s response consists of an immune reaction of anti tissue transglutaminase antibodies with a special form of tissue transglutaminase found in the skin. The lesions will typically form little blisters resembling herpes, hence its name, dermatitis herpetiformis.

Everyone with DH is considered to have a gluten sensitivity (celiac disease). While the majority of people will have an abnormal intestinal biopsy that demonstrates the characteristic changes of celiac disease, in 20% the biopsy can be normal. The diagnosis of DH requires a biopsy of skin immediately adjacent to a blistering lesion. Special studies (immunofluorescence for IgA deposition) are required for diagnosis. The lesions are very sensitive to ingestion of small amounts of gluten. Some patients require therapy with Dapsone to suppress the lesions. This may be used intermittingly and is not needed when patients are adhering to a strict gluten-free diet. Withdrawl of iodine from the diet may be necessary for the gluten-free diet to have a beneficial effect.

Patients with DH are a risk for all the complications that those with celiac disease but not DH experience. These include osteoporosis, iron deficiency anemia and vitamin and mineral deficiencies. Patients should be assessed regularly for these complications and treated accordingly. DH similar to celiac disease is associated with an increased risk of lymphoma. The gluten-free diet will protect against the development of lymphoma whereas Dapsone does not. A common problem is that patients will use Dapsone to control the lesions and not adhere to a gluten-free diet.

Autoimmune damage, the first manifestation of celiac disease, carries with it an array of potential symptoms. But as happens so often in life, one thing leads to another. When the immune system compromises the ability of the small intestine to absorb and transmit nutrients, malnutrition may result. And malnutrition carries its own array of potential disease symptoms. 250 different celiac disease symptoms and related conditions have so far been identified, among them. However the spectrum of the disease is very great with some people obese rather than malnourished.

Celiac Disease –multiple manifestations

Patients often have a vast array of symptoms and complications, not justone symptom. Here is a list which is not exhaustive. Patients with thesesymptoms warrant screening for celiac disease.

Gastrointestinal

• Recurring abdominal pain
• Chronic diarrhea
• Constipation
• Persistent anemia
• Chronic fatigue
• Weight loss
• Osteopenia, osteoporosis and fractures
• Infertility
• Muscle cramps
• Discoloration and loss of tooth enamel

Autoimmune Associations

• Dermatitis herpetiformis (DH)
• Aphthous stomatitis/ulcers
• Peripheral neuropathy, ataxia and epilepsy
• Thyroid disease
• Sjogren’s syndrome
• Chronic active hepatitis, primary biliary cirrhosis, sclerosing
• Cholangitis

Malignancies

• Non-Hodgkin lymphoma (intestinal and extra-intestinal, T- and B-cell types)
• Small intestinal adenocarcinoma
• Esophageal carcinoma
• Papillary thyroid cancer

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