Lactology Foundation

Abdominal Pain from Intoxication

Severe colicky diffuse abdominal cramp pain occurs in lead poisoning. The abdomen may be tense but remains compressible and there is no particular pain upon palpation. There is no rebound tenderness. In principle, all heavy metals can cause abdominal pain. Abdominal pain associated with thallium poisoning is similar to that of lead poisoning and porphyria, which is characterized by persistent constipation and an intermittent pattern.

Porphyrias
Porphyria should be considered in patients with unclear recurring abdominal pain. A positive family history and intermittent occurrence are typical. In some cases the pain can be triggered by drugs and is associated with neurological and dermatological manifestations (photosensitivity). Abdominal colic due to porphyria is frequently misinterpreted, resulting in a surgical intervention.
Pathogenesis
Porphyrias are hereditary disorders of heme metabolism. Porphyrias are classified according to the site of overproduction and accumulation of porphyrin precursors into hepatic and erythropoietic forms. Similar abdominal colics are observed with acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). All three forms can be triggered by drugs. Signs of cutaneous photosensitivity are found with HCP, VP, porphyria cutanea tarda (PCT), and the erythropoietic
porphyrias. In recent years the enzyme defects and underlying genetic mutations responsible for the various forms of porphyria have been identified.

Hepatic Porphyrias
The most important forms of hepatic porphyria are AIP, HCP, VP, and PCT.
Acute Intermittent Porphyria
AIP generally becomes symptomatic in the third decade of life, very rarely before puberty, and is uncommon after the age of 60. The ratio of men to women affected is 2 : 3. Abdominal colic (patients are frequently subjected to laparotomy several times before diagnosis ), often accompanied by constipation or ileus, nausea, vomiting without palpation-sensitive abdomen, motor paralysis as part of a primarily peripheral neuropathy, and cerebral symptoms characterize the variable clinical picture. Often only a slight muscular weakness can be noted. All muscles, including the facial muscles, may be affected. Ascending paralysis occurs. Affection of the respiratory muscles may cause respiratory insufficiency. Paresis may recede. Epileptiform attacks and psychiatric symptoms (anxiety attacks, sleeplessness, depression, hallucinations, etc.) are not unusual. Additional symptoms are tachycardia, hypertension, fever, and moderate leukocytosis. Typically, acute attacks are triggered by barbiturates and other drugs (e. g., sulfonamides, pyrazolone, ergotamine preparations, succinimide, carbamazepine). Alcohol, weight-reduction diets, and endogenous or exogenous sex hormones can also trigger an episode. The urine excreted during an attack darkens and does not
lighten after a few hours, in contrast to normal urine with urobilirubin. Increased excretion of δ-aminolevulinic acid (ALA) and porphyrobilinogen (PBG) in the urine during an acute episode are diagnostic. Unlike HCP and VP, porphyrin excreted in the stool in AIP is generally normal.
In the latent stage diagnosis can be made by the detection of reduced hydroxymethylbilane (HMB) synthetase activity in the erythrocytes.
Hereditary Coproporphyria
Triggering factors, as well as neurovisceral and other symptoms, correspond to those of AIP. Skin photosensitivity is similar to that of VP and PCT. The excretion of coproporphyrin in urine and stool is increased during acute attacks, but often also in the interval. ALA and PBG excretion in the urine is increased during the attacks.
Variegate Porphyria
The incidence of VP among the white population in South Africa is 0.3%, but it is rare in the Western world. Triggering factors and neurovisceral and other symptoms are similar to those of AIP.
Cutaneous photosensitivity is similar to that of HP and PCT. The excretion of ALA, PBG, and coproporphyrin in urine and of coproporphyrin and protoporphyrin in the stool is increased.
Porphyria Cutanea Tarda
PCT is the most common form of porphyria and is observed almost exclusively in men. The skin manifestations (photosensitivity) are dominant. Neurological manifestations and abdominal pain are not observed. Different types are distinguished, but all have a defect of the hepatic uroporphyrinogen decarboxylase in common. Various factors can
contribute to reduced enzyme activity, particularly alcohol use, hepatic iron overload, and estrogens.
Chronic liver diseases (fatty liver, fibrosis, cirrhosis) are frequent and may dominate the clinical picture. Patients with PCT have an increased risk of developing hepatocellular carcinoma.
An association with chronic hepatitis C has been described. Porphyrins in the urine and stool are increased. ALA and PBG excretion in the urine is typically normal.

Erythropoietic Porphyrias
The most important erythropoietic porphyrias are congenital erythropoietic porphyria (CEP) and erythropoietic protoporphyria (EPP).
Congenital Erythropoietic Porphyria
This is an autosomal recessively inherited disease characterized by hemolytic anemia, high-grade photosensitivity of the skin, and accumulation of the type I isomers of uroporphyrin and coproporphyrin. Marked skin changes with blisters, followed by scars and dystrophic changes of body parts exposed to the light dominate the clinical picture, and occur shortly after birth. The red urine contains primarily uroporphyrin I and somewhat less coproporphyrin I. The ratio is reversed in the stool. ALA and PBG excretion is normal. Hemolytic anemia with ineffective erythropoiesis and splenomegaly are typical.
Erythropoietic Protoporphyria
EPP is the second most common form of porphyria after PCT. It is an inherited autosomal dominant disease caused by a defect of ferrochelatase. Protoporphyrin accumulates in the erythrocytes and in the plasma and is excreted in bile and stool. The symptoms are generally mild, transitory skin changes after exposure to sunlight (itching, burning, reddening, urticaria) but may vary from patient to patient and during the course of the disease. Blisters are rare compared with other porphyrias with skin photosensitivity. Hemolysis or anemia is generally not present or only mild. In some patients the accumulation of protoporphyrin causes chronic liver disease. Increased protoporphyrin in the erythrocytes and proto-
porphyrin in the stool are diagnostic. The urine is normal.
Lead Poisoning
Lead poisoning causes a special form of porphyrinuria. In children, encephalopathy is dominant, whereas in adults colic and neuromuscular manifestations predominate. The lead seam on the gums is also typical. Lead anemia is due to hemolysis, caused by direct damage of erythrocytes and inhibition of erythropoiesis. The relative involvement of these two mechanisms is variable. Reticulocytosis can be marked or absent. The characteristic basophile punctation of the erythrocytes corresponds to altered ribosomes. Longer lasting subclinical intoxication can cause deficiencies in intellectual development in children and renal insufficiency in adults. Lead inhibits heme synthesis at various times
levels (ALA synthetase, ALA dehydrase, ferrochelatase). Increased ALA excretion is a typical symptom. Copro porphyrin III excretion is also increased. PBG excretion is generally normal, or at most moderately increased. Erythrocyte protoporphyrin is markedly increased. Diagnosis is confirmed by an increased lead level in the blood or an increased lead excretion in the urine and stool.
Abdominal Pain in Other Medical Diseases
Abdominal pain occurs not only with local diseases, but can also be the leading symptom of many general diseases. The most frequent general diseases that must be considered here are listed below.
Metabolic and Endocrine Diseases
Diabetic precoma is frequently accompanied by severe abdominal pain primarily localized in the epigastric region, and accompanied by severe vomiting. The differential diagnoses, therefore, include perforated ulcer, cholecystitis, and acute pancreatitis. Leukocytosis is common in all these conditions. Patients with acute endocrinologic disorders also frequently experience abdominal cramps, often associated with vomiting or diarrhea. In particular, thyreotoxicosis, acute hyperparathyroidism, and pheochromocytoma must be considered in the differential diag-
nosis of abdominal cramps. Very severe abdominal pain can also be observed in familiar hyperlipidemia (type I, IV, V). If hyperlipidemia is associated with a surgical abdomen, the clinician must search for additional signs: xanthomas, lipemic retinitis, and rarely hepatosplenomegaly. Triglycerides are significantly increased in serum, giving rise to its milky appearance. Transient hyperlipidemia in alcoholics associated
with jaundice and hemolytic anemia - Zieve syndrome; may also lead to severe epigastric pain.
Similar acute pain is observed with alcoholic hepatitis.

Chest Diseases
Pain radiating to the epigastric region is frequent with myocardial infarction, particularly with posterior myocardial infarction.
The diagnosis is straightforward if chest pain is concomitant. It is often overlooked, however, if the pain is exclusively localized in the epigastric region. ECG and laboratory tests usually confirm the diagnosis.
Acute pulmonary diseases, particularly pleuritis, pneumonia, spontaneous pneumothorax, and pulmonary embolism (infarction), can cause abdominal pain. A chest x-ray is usually diagnostic.
Small amounts of free air under the diaphragm can be better detected in the chest x-ray than in the abdominal view.
Liver Diseases
Severe epigastric pain is observed occasionally with various liver diseases, particularly with acute right-sided heart failure, alcoholic hepatitis, and neoplasias of the liver.
Collagen Diseases
These can cause abdominal pain by involving small and medium-sized vessels. Vascular occlusion in systemic lupus erythematosus or panarteritis nodosa results in infarctions (e.g., splenic, pancreatic) or ulcers in the gastrointestinal tract, and corresponding complications (e.g., hemorrhage, perforation, stenosis). Abdominal pain is also observed with various rheu-
matic-allergic diseases, such as Henoch−Schönlein purpura and in Behçet syndrome.
Indeterminate gastrointestinal complaints and signs of ileus, perforation, and peritonitis may be observed primarily in young men with Köhlmeier−Degos syndrome. Diagnostic hallmarks are skin changes (malignant atrophic papulosis) that usually precede gastrointestinal symptoms. The reddish papillae appear on the trunk and the proximal parts of the extremities over days to weeks, they become pale in the center and are surrounded by a slightly raised violet ring with telangiectasia. The cause of the underlying obliterating endothelial reaction of the small arteries, arterioles, and veins is unknown. This rare disease is usually lethal.

 Hematologic Diseases
Abdominal pain in patients with primary hematologic diseases is often caused by complications such as cholelithiasis in congenital spherocytosis, nephrolithiasis in leukemia, splenic infarction in
polycythemia, retroperitoneal or intestinal hematoma in coagulation disorders.
Allergic Diseases
With severe allergic reactions (e.g., serum sickness) abdominal pain may precede other allergic symptoms (e.g., skin changes) in the form of severe continuous pain in the kidney region or as cramplike pain in the epigastric and hypogastric regions.
Infectious Diseases
Abdominal symptoms are frequent in most acute infections and range from loss of appetite to severe pain. The pain associated with Bornholm disease may occasionally be localized primarily in the abdominal region. Abdominal pain may occur in various parasitic infections, particularly trichinosis, ascaridiasis, trichiuriasis, and tapeworm infections.

Neurogenic Abdominal Pain
Abdominal pain may also be a manifestation of a neurological disease. The following syndromes should be considered:
➤ tabes dorsalis (tabetic neurosyphilis)
➤ intercostal neuralgia
➤ proximal asymmetric diabetic neuropathy
➤ entrapment neuropathy of an anterior ramus of a
spinal nerve (T7−T12)
➤ pudendal neuralgia
➤ coccygodynia
➤ radicular syndrome
➤ herpes zoster
Clinical and Differential Diagnostic Considerations
Neurogenic abdominal pain can best be distinguished by the
type of pain.
➤ The stereotypical shooting pain of tabes dorsalis, mostly in the mammary region, is rare.
➤ As indicated by its name, intercostal neuralgia primarily manifests itself with shooting pain, always at the same site. Coughing and sneezing or pressure on the lateral cutaneous ramus sometimes causes pain at its passage. The cause of the pain may be a benign chronic compressive radiculopathy from spinal vertebra that have fused due to degenerative processes, from thoracic disk hernia, rib fracture or thoracotomy. Malignant compressive radiculopathy from metastases, meningeal carcinoma, Schwannoma, or a tuberculous lesion should be considered.
➤ Only in the rare "shingles without shingles" will the acute herpes zoster pain pose diagnostic problems. The abdominal pain precedes blister formation by days. Borreliosis also causes intensive and acute pain in the midsection but without skin changes and can be diagnosed by serology.
➤ Asymmetric diabetic proximal neuropathy (radiculopathy) is frequently not diagnosed. Like borreliosis radiculitis, it frequently begins unilaterally and later appears contralaterally, and tends to occur segmentally, to be localized in the abdominal region and often lasts for months. Many abdominal signs and symptoms are mistakenly attributed to borreliosis because of the frequent severe pain upon touching the skin, with allodynia or hyperpathia. Importantly, diabetes may be only mild. Asymmetric diabetic neuropathy is often associated with a distal symmetric polyneuropathy.
➤ A neuropathy of the anterior rami of spinal nerves T7−T12 by compression of the rectus abdominis muscle or by overextension (e.g., during pregnancy) may cause pain near the abdominal midline. A predisposing polyneuropathy must be considered with such unusual pressure or compression neuropathies.
➤ Perineal and genital lancinating or burning pain with itching, numbness, or painful sensitivity to touch indicate pudendal neuralgia due to a lesion of one or both pudendal nerves, rarely also with an initial caudal or plexus process. Sitting becomes painful and sexual activity impossible. Etiologic factors are obstetric procedures, gynecologic, urologic or proctologic conditions, surgery, perforating trauma, and excessive horse or bicycle riding. Unlike pudendal neuralgia, genitofemoral neuralgia (ventrally) and coccygodynia (dorsally) do not affect the perineal region.
➤ Coccygodynia, burning pain at the coccyx caused in part by (secondary) arachnoidal growth of sacral nerve roots, has primarily mechanical causes such as a direct fall on the coccyx, microtraumatization (television bottom), or surgical procedures.
Nerve blockade or local anesthesia often allow differentiation of this pain.
➤ Pain in the abdominal region is also frequently part of a radicular pain syndrome in various spinal disorders,
particularly spondylarthritis, discopathy, Bechterew disease, osteoporosis, etc.