Part I of this article (J Am Acad Dermatol 1989; 20:537-63) focused on normal sweat gland function. Part II provides a discussion of hyperhidrosis and hypohidrosis. Hyperhidrotic disorders affect the palms and soles and the axillae and are associated with previous spinal cord injuries, peripheral neuropathies, brain lesions, intrathoracic neoplasms, systemic illness, and gustatory sweating. Hypohidrotic disorders include anhidrotic ectodermal dysplasia, hereditary sensory neuropathy, Holmes-Adie syndrome, and generalized anhidrosis.

https://www.jaad.org/article/S0190-9622(89)70081-5/pdf

Biology of sweat glands and their disorders. II. Disorders of sweat gland function.

The heavy metal lead is a widely deposited environmental toxicant known to impact numerous physiological systems, including the reproductive, neurological, hepatic, renal, and immune systems. Studies illustrating the capacity of lead to impair immune function and/or host resistance to disease date back to at least the 1960s. However, it has only been in recent years that lead has been recognized among a new category of immunotoxicants-those that dramatically shift immune functional capacity while producing only modest changes to immune cell populations and lymphoid organs. These relatively noncytotoxic immunomodulating chemicals and drugs represent the immunotoxic hazards most difficult to identify and problematic for risk assessment using historic approaches. As a result, such environmental factors are also among the most likely to contribute to chronic immune-related disease at relevant exposure levels. This review considers the animal and human evidence that lead exposure can produce a stark shift in immune functional capacity with a skewing predicted to elevate the risk of atopic and certain autoimmune diseases. At the same time, host defenses against infectious agents and cancer may be reduced. Age-based exposure studies also suggest that levels of blood lead previously thought to be safe, that is, below 10 microg/dl, may be associated with later life immune alterations.

Lead and immune function.

The fundamental characteristic of the adaptive immune system which has evolved in the vertebrates is the ability to recognise, and subsequently destroy, "foreign", and potentially harmful, antigens. The selective advantage which the immune system confers is the capacity to resist infectious, and possibly malignant, disease. It has been apparent for many years that individuals in whom immune function is impaired, due either to a congenital defect or to other factors such as treatment with certain immunosuppressive drugs, exhibit an increased susceptibility to infection and, in some cases, an elevated risk of developing at least some forms of malignancy. There is an increasing awareness from rodent studies that a variety of drugs and environmental chemicals have the potential to unintentionally impair components of the immune system. Risk assessment, based upon data from chemically induced changes in one or more parameters of immune function, is, however, dependent upon a knowledge of the functional reserve of the immune system. One of the objectives of the meeting from which this report derives was to examine what sources of information are available, and what experimental protocols can be employed, to permit accurate evaluation of immunological reserve. Although, under normal circumstances, the immune system selectively and specifically recognises foreign antigen, it is clear that the potential to recognise "self" is present and that in certain circumstances this potential is realised. Antibodies directed against normal tissue antigens have been shown to be associated with, and in some instances the presumptive cause of, "autoimmune" disease. There is a growing list of drugs and chemicals which are capable of eliciting autoantibodies and pathological autoimmune reactions. A second purpose of this meeting and of this report was to review the current state of knowledge regarding drug- and chemical-induced autoimmunity.

Immunotoxicology: suppressive and stimulatory effects of drugs and environmental chemicals on the immune system - A discussion

Evidence implicating oxidative stress in toxicity during lead intoxication in vivo has opened new avenues for investigation of the mechanisms of lead-induced immunosuppression. The current study explores the possibility that lead-induced oxidative stress contributes to the immunosuppression observed during lead poisoning. Fisher 344 rats were exposed to 2,000 ppm lead acetate in their drinking water for 5 weeks. One week following removal of lead from the drinking water, significant reductions in serum levels of IgA, IgM, and IgG were detected. Significant increases in oxidative damage, based on malondialdehyde (MDA) content, were observed in peripheral blood mononuclear cells (PMCs) collected during the same experiments. In addition, MDA content increased in livers from lead-exposed rats. Following 5 weeks of lead exposure, administration of either 5.5 mmol/kg N-acetylcysteine (NAC) or 1 mmol/kg meso-2,3-dimercaptosuccinic acid (DMSA) in the drinking water for 1 week significantly reversed the inhibitory effects of lead on serum immunoglobulin (Ig) levels. Also, all parameters indicative of oxidative stress returned to control levels. These results suggest that oxidative stress contributes to suppressed serum Ig levels during lead intoxication in vivo, and that intervention with either a thiol antioxidant (NAC) or a metal chelator (DMSA) will alleviate this lead-induced suppression by correcting the prooxidant/antioxidant imbalance caused by lead exposure.

/pdf/a-role-for-oxidative-stress-in-suppressing-serum-hy6wjqhq3f.pdf

A role for oxidative stress in suppressing serum immunoglobulin levels in lead-exposed Fisher 344 rats.

Effect of lead exposure on the immune response of some occupationally exposed individuals

Effect of low-level lead exposure on antibody-dependent and natural killer cell-mediated cytotoxicity

This report describes a patient with localized unilateral hyperhidrosis secondary to malignant mesothelioma and discusses the pathophysiology involved. REPORT OF A CASE A 35-year-old man experienced severe pleuritic-type pain in the right anterior portion of the chest for six months before admission to the hospital. He also had anorexia, malaise, and a 9-kg weight loss. One month before admission he suffered profuse sweating of his face and right upper torso, including his right arm, that was unrelated to eating, hunger, sleep, urination, or defecation. The sweating became so severe that the patient slept with towels wrapped around his arm and changed his pajamas several times during the day. He had not had tuberculosis, diabetes, rheumatic fever, hypertension, or cardiac distress. He had worked in Italy pouring concrete, but denied exposure to asbestos or excessive dust. He did not smoke or drink alcohol. On admission to Temple University Hospital, Philadelphia, he

Paroxysmal unilateral hyperhidrosis and malignant mesothelioma.

Natural cell-mediated cytotoxicity in cutaneous T-cell lymphomas.

• Phenytoin sodium has been associated with the formation of altered T lymphocyte rosettes in vitro. To investigate the clinical relevance of this observation, the formation of T lymphocyte rosettes in nine patients was studied before treatment with phenytoin and after therapeutic concentrations of the drug in plasma were attained. The percentage of total rosette-forming cells found before treatment was not significantly different from the percentage found 24 hours after treatment. Likewise, the percentage of active rosette-forming cells before phenytoin therapy was not significantly less than after therapy. These results suggest that in vivo treatment with phenytoin does not acutely inhibit the formation of T lymphocyte rosettes.

Barbara A. Neilan

Papers

Effect of low-level lead exposure on antibody-dependent and natural killer cell-mediated cytotoxicity

Paroxysmal unilateral hyperhidrosis and malignant mesothelioma.

Natural cell-mediated cytotoxicity in cutaneous T-cell lymphomas.

Phenytoin and Formation of T Lymphocyte Rosettes

Further investigation of methylation on sickle erythrocyte membranes