The previous chapters outlined in detail the aetiological factors in acne and the way in which they may produce the various physical signs associated with this disease. The  aim of  this chapter is succinctly to link these preceding chapters to provide an overall view as to the possible cause of acne.

 

  There is no doubt whatsoever that androgens are a prerequisite  for  acne.  Under  the  influence  of androgens,  in  particular  testosterone and   dehydroepiandrosterone, the sebaceous glands increase in size and  produce  sebum. In acne  patients,  despite  the wealth of literature suggesting that many female  patients have high levels of circulating  androgens, this author strongly believes that the increased sebum production, characteristic of patients with acne is often due to end-organ hyperresponse of the sebaceous gland to the normal levels of circulating androgens. The reason for this is predominantly the view that acne, although possibly severe at one body site, such as the back of one patient,  may be associated with little  or  no acne at another  site in the same patient. Furthermore, manymales have certain androgens present in much higher levels than females and  yet not all males have acne. Thirdly, there is no correlation between acne severity and clinical features of androgenicity.  Although small numbers of acne females may, indeed, have significant abnormalities in their plasma hormones, in the average acne patient there is no need to investigate for evidence of hyperandrogenicity.

 

  Patients with acne have an increased  sebum production (seborrhoea) which is related to the severity of the disease.  They also exhibit noninflamed and  inflamed lesions. The noninflamed lesions may be whiteheads or blackheads; these  represent distention of the  pilosebaceous duct. Why some follicles in  an  acne-prone individual  develop these hypercornified lesions is not fully understood. Nor is it known why some lesions develop into whiteheads and others blackheads. Whiteheads outnumber blackheads by about seven to one.

 

  It  appears likely from ongoing research, that the pilosebaceous duct is also under androgen control. This would not be surprising because of the close anatomical links  between  the  sebaceous gland and  the pilosebaceous duct. Some years ago it was  suggested that certain components of sebum, in particular certain fatty acids, squalene and squalene oxide, may be comedogenic. This evidence emanates predominantly from the rabbit ear  model which, though overpredictive, could nevertheless  be  a guide. Recent  work  from the USA suggests that comedone formation may be due to a localized deficiency of linoleic acid in the pilosebaceous duct.  Linoleic acid is an essential fatty acid;  animals deficient of linoleic acid become scaly.  The comedone really represents abnormal  accumulation of cornified cells. It is suggested that the essential fatty acid linoleic acid is incorporated via the plasma into the sebaceous gland cells. As these divide and eventually disintegrate, linoleic acid  becomes incorporated  into the  sebum. Because of the  large volume of sebum  present in the sebaceous  system of acne patients, there is  a dilution effect: the  ductal corneocytes are effectively bathed in an inadequately low level of linoleic acid.

 

  The  use of special  Sebotape  and of the follicular biopsy technique (which samples the  upper part of the duct) indicate that the increased sebum excretion rate and microcomedone formation  is occurring  in and around the sites where there are obvious clinical lesions. Thus, in the  investigation of acne patients, it is preferable to investigate these early primordial events rather than established lesions. Acne is a disease of individual pilosebaceous follicles and, although considerable information has been derived by analysing events  on the surface of the skin, more would be discovered about acne by investigating the individual follicles.

 

  This suggestion is confirmed by work which relates acne  and cutaneous  bacteria.   Skin  surfaces  in  the acne-prone areas  are  colonized with  Staphylococcus epidermidis  and  Propionibacterium acnes. Selective inhibitory studies  suggest that the main organism is P. acnes. Using biopsy techniques  and the surface biopsy methods to obtain organisms from the upper part of the duct, it is now clear that bacteria have nothing whatsoever to do  with the  initiation of  comedogenesis. However, biopsies of early, timed inflamed  lesions suggest  that  P.  acnes,  in  particular,  may  in some situations be important in the initiaton of inflammation. It  is  also quite  likely that they are  involved  in  a perpetuation of inflammation once established.

 

  Recent work  analysing biopsies whose time from onset of inflammation is known  have demonstrated quite clearly the dynamic histological event resulting in acne inflammation. The early cellular infiltrate  is lymphocytic; this is seen around the blood vessels and the duct. Within 12-24 hours polymorphonucleocytes also become evident, but the lymphocyte usually remains in papules as the predominant  cell infiltrate.  Ductal rupture is not a prerequisite for the  development of inflammation in that up to 80 per cent of early inflamed acne lesions arise without rupture of  the duct. This suggests that in  the  initiation  of many inflamed lesions  the induction  of inflammation  is  due to  the release of substances from within the duct which escape into the dermis stimulating chemotaxis which produces inflammation. The source of these mediators could be P. acnes or  their  extracellular products. Alternatively,  they could arise from the eukarytotic cells,  i.e. the ductal keratinocytes.  Keratinocytes are a known  source of cytokines. Stimulation of complement - both the alternative classical pathways  - are evident too in the early stages of inflammation but no data are yet available to indicate where the complement  system is stimulated in the first  1-2 hours.  It is definitely  activated  twelve hours after the initiation  of an inflammatory lesion.

 

  The  host  response   to  these  mediators  is  also important.  Patients with more  severe acne show, on skin testing, an enhanced response to P. acnes antigens. In  late-stage  inflammation,  especially  with  the larger papules and nodules, there  is gross disruption  of the pilosebaceous  system.  The  cornified cells containing the highly insoluble keratin and  the  lipid from  the sebaceous gland are highly irritant and help to produce a nonspecific reaction associated with macrophages and giant cells.

 

  The inflammation is  not, in most patients, an abnormal response of the immune system. The inflammation represents a normal immune and nonimmune response to foreign substances penetrating the dermis.  Acne is not infectious and this is important to stress to patients.

 

  In most instances the inflammation  settles, papules and pustules lasting about 3-14 days but larger lesions persist longer. The larger, and more actively inflamed, lesions will, in some  instances, produce permanent dermal damage and result in scarring. Why some scars are hypertrophic and others are atrophic is not known but certain sites show certain predilections. For example, areas of the skin which are more easily stretched, such as the upper back, are more prone to  develop atrophic scars.

 

  One of the enigmas of acne is why, in most patients, it improves in the  early twenties and, in most patients but not all, is resolved at the age of 25. It is certainly not due to a reduction in  sebum excretion rate nor  to  a reduction in skin  surface P. acnes. As  indicated  previously, attention  should  be given to the follicle. It could be  that the  resolution of acne  is related  to  a change in  response in the  follicle,  which no longer produces  hypercornification. An alternative explanation is a change in the host response to various inflammatory stimuli but, as  the noninflamed as well as the inflamed lesions disappear as the acne resolves, it seems most likely that the resolution of the acne  is related to specific changes in duct function.

 

  Thus,  although  the precise mechanisms  of acne are not known, it is clearly accepted that  there are these four major aetiological  factors involved  in its development: 

1. an  increased sebum  excretion;
2. ductal hypercornification;
3. colonization of the duct with P. acnes;  and 
4. further production  of  inflammation.

Drug  regimens which  affect these aetiological factors improve  acne  and drugs,  such as isotretinoin, which affect all these factors, have a greater effect on acne than other modalities.

 

  The next few chapters discuss, in detail,  the management  of acne patients, including that of the therapeutically difficult patient and the side-effects of acne therapy.