Alopecia areata and humpy-back syndrome in suckling piglets

Abstract

This report describes an uncommon variant of humpy-back syndrome associated with multiple rib fractures and multisystemic vasculitis in several nursing piglets and, for the first time, a skin disease in swine consistent with alopecia areata. Both conditions were observed concurrently on the farm and occasionally in the same piglets.

Alopecia areata (AA) is a non-scarring, asymptomatic, inflammatory alopecia observed in humans, dogs, cats, horses, cattle, and nonhuman primates as well as in mice and rats which are used as models to study the condition (1–3). Alopecia areata may be focal, multifocal, or generalized (alopecia universalis). The histological hallmark of the early stage of this putative autoimmune skin disease is the infiltration of inflammatory cells, mostly T-lymphocytes, in and around the bulb (bulbitis) of the anagen hair follicles (4). Occasionally inflammation may progress superficially to include the isthmus of the follicles (4,5). In animals, AA is a cosmetic disease and does not affect the quality of life (4,5).

Another condition named “humpy-back syndrome” has been reported in pigs in several countries (6–9). This conformation problem is characterized by an upward curvature of the lumbar spine (kyphosis) and downward curvature of the thoracic spine (lordosis). This deformity of the back is most often observed at 8 to 16 wk of age, but in some cases it may be detected as early as 3 wk of age. The severity of the condition is variable but severely affected animals often have to be euthanized for humane reasons. There are at least 4 variants of the syndrome, one of which is associated with multiple rib fractures and multisystemic vasculitis (7,9,10). Various causes for this syndrome have been proposed.

The present report describes an uncommon variant of humpy-back syndrome in several nursing piglets, which was associated with multiple rib fractures and multisystemic vasculitis, and for the first time, a skin disease in swine consistent with alopecia areata. Both conditions were observed concurrently on the farm and even in the same piglets.

Case description

A health problem was reported in a newly populated 1600-sow herd, on a 2-week batch system with a weaning age of 20 d. The swine producer complained about having nursing piglets with hairless patches (alopecia) and abnormal back conformation (humpy-back). Eight litters from parity 1 and 2 sows were involved over a 6-week period, representing approximately 2% of sows at risk for that period. A total of 21 piglets of both sexes were affected, 10 with alopecia only, 5 with humpy-back, and 6 with both conditions (Table 1). Typically, 1 to 3 piglets per litter were affected, but 1 litter had up to 8 affected piglets. Lesions of alopecia were reported to be observed at birth in at least 6 piglets from 3 litters, whereas in others they were detected later, before weaning. Humpy-back piglets were generally observed at more than 10 d of age and most of these piglets had to be euthanized for humane reasons because they were doing poorly or had developed dyspnea. Although the herd was repopulated with a high-health breeding stock, it had experienced an outbreak of porcine reproductive and respiratory syndrome (PRRS) when the first sows due to farrow were moved into the farrowing house. There were still animals with clinical signs in the herd when sows of the affected litters were in their first 3 mo of gestation. Sows and gilts had been vaccinated for parvovirus, Leptospira spp., Erysipelothrix rhusiopathiae, and Escherichia coli; when they were 6 to 8 mo old, gilts also received a vaccine against porcine circovirus type 2 (PCV2), influenza, Mycoplasma hyopneumoniae, Haemophilus parasuis, and Lawsonia intracellularis. No other cases were observed during the 7 mo that followed this outbreak.

Table 1.

Number of affected piglets and litters based on gross lesions

	Alopecia only	Humpy-back only	Alopecia and humpy-back	Total
Affected piglets	10	5	6	21
Age of affected piglets
Newborn	6	0	0	6
> 1 and < 3 wk	2	3	5	10
Unknown	2	2	1	5
Affected litters	4	2	2	8

Four 2-week-old piglets from the same litter were submitted for necropsy. These piglets were euthanized on-farm because they exhibited the back problem, and 3 of them also had cutaneous alopecia. Necropsies were performed on these 4 piglets and various organs and tissues were selected from 2 piglets for routine histopathology, and bacteriological and virological examination. Skin samples from the 3 piglets with cutaneous lesions were also examined histologically. Grossly, all piglets had abnormal conformation of the back characterized by lordosis of the thoracic vertebral column (behind the shoulder) and kyphosis of the lumbar spine (Figure 1). Other than an abnormal curvature of the vertebral column, vertebrae and musculature around the vertebrae appeared normal. All piglets examined also had multiple rib fractures with at least 6 fractures on each side of the rib cage. These chronic rib fractures, with firm nodular calluses up to 1 cm in diameter, were often located either at mid-shaft level or in the lower third of the ribs in the mid-thoracic regions, sparing the first and last ribs (Figure 2). Costochondral junctions were not affected and bones away from the fracture sites appeared normal. Upon examination of the skin, 3 piglets had multifocal round foci of alopecia measuring a few millimeters to 1 cm in diameter, affecting mainly and asymmetrically the trunk and the lateral aspect of the limbs (Figures 3 and 4). Some of the smaller foci were difficult to detect particularly when the skin was wet.

Figure 1.

Two-week-old piglet with abnormal curvature of the vertebral column (arrow).

Figure 2.

Right thoracic rib cage of a 2-week-old piglet showing 8 adjacent rib fractures with prominent calluses. Costochondral junctions were not affected.

Figure 3.

Two-week-old piglet with small round foci of alopecia (arrows).

Figure 4.

Two-week-old piglet with a closer view of an area of alopecia of about 1 cm on the lateral aspect of the left thigh.

Histologically, tissues from both piglets examined had similar lesions. Lesions of vasculitis were present in many internal organs and tissues. They involved mainly small to medium-sized arterial blood vessels and were characterized by infiltration of the tunica adventitia and to a lesser extent the media by lymphocytes, lymphoblasts, and fewer plasmocytes and histiocytes. Occasional necrotic debris was also noted in the tunica media (Figure 5). Tissues affected with these vascular lesions included cerebrospinal meninges, heart, skeletal muscles, lungs, liver, kidneys, lymph nodes, gastrointestinal tract, mesentery, omentum, and soft tissues around bones including the ribs. Other lesions observed included a mild non-suppurative interstitial pneumonia, myocarditis and myositis. Calluses present at the rib fracture sites were composed of cartilage and to a lesser extent bone tissue. The other bones examined, including femurs and vertebrae, appeared normal with no evidence of metabolic bone disease such as rickets, osteoporosis or osteochondrosis.

Figure 5.

Omentum of an affected piglet showing lymphocytic arteritis involving mainly the tunica adventitia. Hematoxylin-eosin-phloxine-saffron (HEPS) stain. Bar = 50 μm.

The 3 piglets with alopecia on gross examination showed microscopic skin lesions that mainly involved the hair follicles. The follicular lesions were characterized by a lymphocytic inflammation located in and around the anagen hair bulbs (lymphocytic bulbitis and peribulbitis). The lymphocytic inflammation encircling the affected bulbs was occasionally accompanied by some plasmocytes and histiocytes. In some areas there was also a mural lymphocytic folliculitis affecting the isthmus (Figure 6). In 1 section examined, some follicles had completely disappeared without leaving any scar. Immunohistochemical staining of skin samples with anti-CD3 (Polyclonal rabbit anti-human CD3, Dako North America, Carpinteria, California, USA) revealed that most inflammatory cells present in and around anagen hair bulbs and isthmus were T-lymphocytes (Figure 7).

Figure 6.

Skin of an affected piglet: Lower part of a hair follicle showing lymphocytic bulbitis and peribulbitis and some focal mural folliculitis (upper left). HEPS stain. Bar = 50 μm.

Figure 7.

Skin of an affected piglet: Immunohistochemistry for CD3 indicates that most cells in and around this severely inflamed hair follicle bulb are T-lymphocytes. Bar = 50 μm.

Bacterial examination of lung, liver, and spleen from 2 piglets yielded no or insignificant growth. Pools of lung and lymphoid tissues from each of these 2 piglets were negative for PCV2 and PRRS virus using a quantitative polymerase chain reaction assay (11).

Discussion

The histological and immunological findings in the skin of these piglets are consistent with a diagnosis of AA. The characteristic lesion of AA is a lymphocytic bulbitis affecting anagen hair follicles with T-lymphocytes being the main cell type involved in the inflammation. In some cases in the dog and horse, significant lymphocytic inflammation involves both the bulb and the follicular wall to the level of the isthmus (4,5). This was also observed in the piglets of this report. It is unknown if these latter lesions are associated with a distinct clinical subtype of AA. The case presented in this report is unusual not only because it represents the first description of AA in the porcine species but also because of the young age of the affected piglets and the fact that it involved several animals, some from the same litter.

The cause of AA is still undetermined but it is suspected to be a genetically predisposed autoimmune disease centered on the lower portion of the hair follicles. It represents a combination of cellular and humoral immunological assaults directed against various follicular components (12). In humans, a high frequency of occurrence within families sharing some human leukocyte antigens (HLA) suggests genetic predilection (2). From the rodent models it has been shown that the development of AA relies on a general genetic susceptibility where major susceptibility genes may be supplemented by minor disease severity modifying genes (3). However, the onset of AA, its duration, extent, severity and persistence in individual rodents may be modified by epigenetic factors. These proven or suspected epigenetic modifiers include diet, hormones, cross-reactive exogenous antigens, and general viral and vaccine load. The role of genetics in the case reported herein could not be demonstrated, although it remains possible since the disease occurred in littermates.

Occurrence of temporary sporadic outbreaks of kyphosis and lordosis, referred to as humpy-back syndrome, has been observed in many countries in recent years. The prevalence of the syndrome in these outbreaks has been reported as 2.5% or less to up to 30% of pigs (9). In most affected animals, the condition is not present at birth, but becomes recognizable at 8 to 16 wk of age and sometimes as early as a few weeks of age (13). The severity of the back deviation has previously been graded into 5 classes (6). Severely affected animals may grow poorly and fail to reach slaughter weight or have to be euthanized for humane reasons. Possible causes of kyphosis and lordosis suggested in pigs include primary vertebral lesions due to physical or metabolic abnormalities, nutritional deficiencies, intrauterine infections, early onset of puberty in male pigs, stress on the lumbar spine caused by painful musculoskeletal conditions, and genetics, but most of them have yet to be confirmed (9,14).

Although much has to be learned about humpy-back syndrome, it has been tentatively classified into at least 4 variants (7,9,10). It is not known if there are overlaps between these variants or if lesions observed in a particular variant may progress to another category with time. In the first variant there may be no significant lesion associated with the deviation of the vertebral column other than a possible mild opening up of intervertebral disk spaces (6,13). In the second, the defect may be associated with the formation of ventral hemivertebrae due to the absence of ventral vertebral epiphyseal centers of ossification (8,15). A third variant of humpy-back syndrome, suspected to involve genetic factors, is associated with increased muscle masses and subsequent disc protrusion (10). Finally another variant of kyphosis and lordosis has been observed in several Canadian herds (7). This fourth variant is associated with multiple rib fractures and a multisystemic lymphocytic arteritis as observed in the piglets of the present report. These rib fractures and the multisystemic vasculitis have not, to our knowledge, been reported in the 3 other variants of the syndrome. The cause of the vascular lesions has not been determined but it has been suspected that viral (e.g., PCV2) infection in utero could be setting up blood vessels of fetuses for an immunologic type II or type IV hypersensitivity reaction (7). To date, piglets examined with this variant of the syndrome, including those of this report, were found to be virus negative for either PCV2 or PRRS virus, 2 of a variety of porcine viruses that can cross the placental barrier and infect piglets in utero (7). However, the herd involved in the report had experienced an outbreak of PRRS that had lasted 4 mo to end approximately 1 mo prior to the birth of the first affected piglets. The pathogenesis of the vertebral defect and rib fractures in relation to these vascular lesions also remains undetermined. There was no report of traumatic events that could have triggered the rib fractures in piglets of the present case.

Any co-relationship between the 2 conditions described in this report (AA and humpy-back syndrome) could not be determined. There were piglets in the herd that were affected with the humpy-back syndrome that did not have the problem of alopecia and vice-versa. For reasons of economy, piglets affected with only the asymptomatic alopecic condition were not submitted for necropsy. It is, however, interesting to note that the lesions of AA as well as the vasculitis observed in the piglets with the back deformity might both have an immunological background. In humans, cases of AA have frequently been reported along with other coexisting immune-mediated diseases (2).